Prediction of breast cancer and axillary positive-node response to neoadjuvant chemotherapy based on multi-parametric magnetic resonance imaging radiomics models.

PURPOSE: Accurate identification of primary breast cancer and axillary positive-node response to neoadjuvant chemotherapy (NAC) is important for determining appropriate surgery strategies. We aimed to develop combining models based on breast multi-parametric magnetic resonance imaging and clinicopathologic characteristics for predicting therapeutic response of primary tumor and axillary positive-node prior to treatment. MATERIALS AND METHODS: A total of 268 breast cancer patients who completed NAC and underwent surgery were enrolled. Radiomics features and clinicopathologic characteristics were analyzed through the analysis of variance and the least absolute shrinkage and selection operator algorithm. Finally, 24 and 28 optimal features were selected to construct machine learning models based on 6 algorithms for predicting each clinical outcome, respectively. The diagnostic performances of models were evaluated in the testing set by the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: Of the 268 patients, 94 (35.1 %) achieved breast cancer pathological complete response (bpCR) and of the 240 patients with clinical positive-node, 120 (50.0 %) achieved axillary lymph node pathological complete response (apCR). The multi-layer perception (MLP) algorithm yielded the best diagnostic performances in predicting apCR with an AUC of 0.825 (95 % CI, 0.764-0.886) and an accuracy of 77.1 %. And MLP also outperformed other models in predicting bpCR with an AUC of 0.852 (95 % CI, 0.798-0.906) and an accuracy of 81.3 %. CONCLUSIONS: Our study established non-invasive combining models to predict the therapeutic response of primary breast cancer and axillary positive-node prior to NAC, which may help to modify preoperative treatment and determine post-NAC surgery strategy.

Path Analysis of Self-Efficacy, Coping Style and Resilience on Depression in Patients with Recurrent Schizophrenia.

Purpose: Based on the two mediating variables of self-efficacy and coping style, a multiple mediating model was constructed to explore the mechanism by which psychological resilience affects depression in patients with recurrent schizophrenia. Methods: A total of 210 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, were enrolled. The Connor Davidson Resilience Scale (CD-RISC), Self-rating Depression Scale (SDS), General Self-Efficacy Energy Scale (GSES) and Simplified Coping Style Questionnaire (SCSQ) were used to evaluate resilience, self-efficacy, coping style and depression. Path analysis was performed by constructing a structural equation model, and the mediating effect between variables was verified by the bias-corrected nonparametric percentile bootstrap method. Results: Resilience, self-efficacy and positive coping together explained 53.2% of the variance in depression. (1) The total scores of self-efficacy, coping style, resilience and depression in patients with recurrent schizophrenia were 2.54±0.61, 31.73±9.62, 58.06±17.26 and 50.48±12.55, respectively. (2) Pearson analysis showed that the scores of self-efficacy, positive coping, resilience and depression were significantly correlated with depression (r=-0.24-0.51, P<0.01). (3) The path analysis showed that resilience directly affects depression (ß=-0.401); additionally, resilience indirectly affects depression through self-efficacy (ß=-0.179) and through the chain mediating effect of self-efficacy and positive coping style (ß=-0.024). Conclusion: There is a high incidence of depression in patients with recurrent schizophrenia in China, and intervention is needed. This research revealed that resilience directly affects depression in patients with recurrent schizophrenia and that self-efficacy and positive coping play a part in mediating resilience and depression in patients with recurrent schizophrenia in China. Implementing targeted interventions based on action paths to improve the level of resilience and reduce the incidence of depression has guiding significance in the field of occupational rehabilitation of patients with recurrent schizophrenia.

New insights into breast microcalcification for poor prognosis: NACT cohort and bone metastasis evaluation cohort.

OBJECTIVES: The study aimed to analyze the poor prognosis of microcalcification in breast cancer (BC), including the pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) and the risk of bone metastases. MATERIALS AND METHODS: 313 breast cancer patients received NACT to evaluate pCR and 1182 patients from a multicenter database to assess bone metastases were retrospectively included. Two groups were divided according to the presence or absence of mammography microcalcification. Clinical data, image characteristics, neoadjuvant treatment response, bone involvement, and follow-up information were recorded. The pCR and bone metastases were compared between subgroups using the Mann-Whitney and χ2 tests and logistic regression, respectively. RESULTS: Mammographic microcalcification was associated with a lower pCR than uncalcified BC in the NACT cohort (20.6% vs 31.6%, P = 0.029). Univariate and multivariate analysis suggested that calcification was a risk factor for poor NACT response [OR = 1.780, 95%CI (1.065-2.974), P = 0.028], [OR = 2.352, 95%CI (1.186-4.667), P = 0.014]. Microcalcification was more likely to be necrosis on MRI than those without microcalcification (53.0% vs 31.7%, P < 0.001), multivariate analysis indicated that tumor necrosis was also a risk factor for poor NACT response [OR = 2.325, 95%CI (1.100-4.911), P = 0.027]. Age, menopausal status, breast density, mass, molecular, and pathology type were not significantly associated with non-pCR risk assessment. In a multicenter cohort of 1182 patients with pathologically confirmed BC, those with microcalcifications had a higher proportion of bone metastases compared to non-calcified BC (11.6% vs 4.9%, P < 0.001). Univariate and multivariate analysis showed that microcalcification was an independent risk factor for bone metastasis [OR = 2.550, 95%CI (1.620-4.012), P < 0.001], [OR = 2.268(1.263-4.071), P = 0.006)]. Osteolytic bone metastases predominated but there was no statistical difference between the two groups (78.9% vs 60.7%, P = 0.099). Calcified BC was mainly involved in axial bone, but was more likely to involve the whole-body bone than non-calcified BC (33.8% vs 10.7%, P = 0.021). CONCLUSION: This study provides important insights into the poor prognosis of microcalcification, not only in terms of poor response to NACT but also the risk factor of bone metastases.

Mediating Effect of Self-Efficacy on the Relationship Between Perceived Social Support and Resilience in Patients with Recurrent Schizophrenia in China.

Purpose: To explore the mediating effect of self-efficacy on the relationship between perceived social support and resilience in patients with recurrent schizophrenia in China. Patients and Methods: In this cross-sectional study, a total of 176 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, completed a general data questionnaire, the Connor Davidson Resilience Scale (CD-RISC), the Perceived Social Support Scale (PSSS) and the General Self-Efficacy Energy Scale (GSES). Results: Among the 176 patients, the mean GSES score was 2.02±0.61, the mean PSSS score was 56.77±14.61, and the mean CD-RISC score was 58.06±17.26. Self-efficacy played a partial mediating role between social support and resilience, and the mediating effect accounted for 42.56% of the total effect. Conclusion: The resilience level of patients with recurrent schizophrenia in China is moderate and needs to be improved. This research revealed that self-efficacy played a part in mediating perceived social support and resilience in patients with recurrent schizophrenia in China. Perceived social support can indirectly affect resilience in patients with recurrent schizophrenia through self-efficacy. Comprehensive interventions in perceived social support and self-efficacy would help to improve the resilience of patients with recurrent schizophrenia.

Metabolomics and Cytokine Analysis for Identification of Schizophrenia with Auditory Hallucination.

PURPOSE: To investigate the metabolic profile and biomarkers of schizophrenia with auditory hallucinations (AHs). METHODS: A total of 18 schizophrenic patients with the symptom of pure AHs (pAHs), 28 without AH (nAHs) and 43 age-matched healthy persons (Con) were enrolled in this study. Participants in pAHs and nAHs groups had relapsed into exacerbations of psychosis after self-discontinuing antipsychotics for at least one month; blood samples were drawn prior to restarting anti-psychotic treatment. Participants with history of recreational substance use were excluded. Positive and Negative Syndrome Scale (PANSS) and Auditory Hallucinations Rating Scale (AHRS) were used to assess the clinical mental state of all samples. Enzyme-linked immunosorbent assay (ELISA) was used to estimate the level of cytokines, and metabolomics analysis to identify potential biomarkers and pathways in the three groups. Graphpad 8.0 software was used to calculate the area under the receiver operating characteristic (ROC) curve. The relationship between metabolites and cytokines were determined using correlation analysis. RESULTS: Questionnaire scores showed significant differences in the positive symptom scale and PANSS total between nAHs and pAHs groups. Four cytokines (BDNF, IL-2, NGF-ß and TNF-α) differed significantly among the three groups. Six molecules in the nAHs group (phenylalanine, hippurate, serine, glutamate, valine and cystine) and four in the pAHs group (phenylalanine, serine, glutamate and cystine) were identified as potential biomarkers. In addition, phenylalanine was shown as a potential independent diagnostic biomarker for pAHs. Correlation analysis revealed that cystine and serine were significantly negatively correlated with IL-2 in the pAHs group. CONCLUSIONS: This study revealed the metabolic profile of patients with schizophrenia with AHs and provided new information to support the diagnosis. The identification of unique biomarkers would contribute to objective and reliable diagnoses of patients with schizophrenia with AH.

Elevated Risk of Venous Thromboembolism in People Living with HIV.

Human immunodeficiency virus (HIV) has been generally considered as a highly adaptive and rapidly evolving virus. It still constitutes a major public health problem all over the world despite an effective outcome in the prevention and reversal of the development and prognosis by using antiretroviral therapy. The salient question lies in the more frequent emergence of a series of comorbidities along with the prolongation of the life, which deeply affects the survival in such group. Venous thromboembolism (VTE) has been recognized to be the third most common cardiovascular condition within people living with HIV (PWH). In terms of its mechanism of action, the occurrence of VTE is quite multifactorial and complex in HIV. Prior exploration concerning the etiology of VTE in PWH identifies general, disease-specific, and miscellaneous factors for explaining its occurrence and development. VTE has constituted an important role in PWH and may increase its all-cause mortality. Therefore, it is quite necessary to understand VTE from the following aspects of epidemiology, pathophysiology, molecular mechanisms, and therapeutic interventions so as to balance the risks and benefits of anticoagulation and optimize corresponding treatment.

Wolbachia wAlbB remains stable in Aedes aegypti over 15 years but exhibits genetic background-dependent variation in virus blocking.

The ability of the maternally transmitted endosymbiotic bacterium Wolbachia to induce cytoplasmic incompatibility (CI) and virus blocking makes it a promising weapon for combatting mosquito-borne diseases through either suppression or replacement of wild-type populations. Recent field trials show that both approaches significantly reduce the incidence of dengue fever in humans. However, new questions emerge about how Wolbachia-mosquito associations will co-evolve over time and whether Wolbachia-mediated virus blocking will be affected by the genetic diversity of mosquitoes and arboviruses in the real world. Here, we have compared the Wolbachia density and CI expression of two wAlbB-infected Aedes aegypti lines transinfected 15 years apart. We have also assessed wAlbB-mediated virus blocking against dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) viruses and examined whether host genetic backgrounds modulate viral blocking effects by comparing ZIKV infection in mosquitoes with a Mexican genetic background to those with a Singaporean background. Our results show that over 15 years, wAlbB maintained the capacity to form a stable association with Ae. aegypti in terms of both density and CI expression. There were variations in wAlbB-induced virus blocking against CHIKV, DENV, and ZIKV, and higher inhibitory effects on ZIKV in mosquitoes on the Singaporean genetic background than on the Mexican background. These results provide important information concerning the robustness and long-term stability of Wolbachia as a biocontrol agent for arbovirus disease control.

Relationship between stressful life events, coping styles, and schizophrenia relapse.

This study aimed to explore the relationship between stressful life events, coping styles, and schizophrenia relapse. The sample for this study included 248 patients with schizophrenia from a psychiatric outpatient clinic in Hunan Province, China. Stressful life events, occurrence of schizophrenia relapse, and coping style were assessed by the Scale for the Social Readjustment Rating, Brief Psychiatric Rating Scale, and Simplified Coping Style Questionnaire, respectively. Spearman correlation analysis and binary logistic regression analysis were adopted to explore the relationships among coping styles, schizophrenia relapse, and stressful life events. Stressful life events and negative coping exhibited significant positive association with schizophrenia relapse, while positive coping exhibited a significant negative association with schizophrenia relapse. Stressful life events and positive coping exerted significant effects on schizophrenia relapse, while negative coping did not. We also found that both positive coping and negative coping have moderating effects on the relationship between stressful life events and schizophrenia relapse, but the relationship is weak. The study highlighted the importance of interventions designed to reduce stressful life events, promote positive coping, and address negative coping in patients with schizophrenia.

Prevalence of simian malaria parasites in macaques of Singapore.

Plasmodium knowlesi is a simian malaria parasite currently recognized as the fifth causative agent of human malaria. Recently, naturally acquired P. cynomolgi infection in humans was also detected in Southeast Asia. The main reservoir of both parasites is the long-tailed and pig-tailed macaques, which are indigenous in this region. Due to increased urbanization and changes in land use, there has been greater proximity and interaction between the long-tailed macaques and the general population in Singapore. As such, this study aims to determine the prevalence of simian malaria parasites in local macaques to assess the risk of zoonosis to the general human population. Screening for the presence of malaria parasites was conducted on blood samples from 660 peridomestic macaques collected between Jan 2008 and Mar 2017, and 379 wild macaques collected between Mar 2009 and Mar 2017, using a Pan-Plasmodium-genus specific PCR. Positive samples were then screened using a simian Plasmodium species-specific nested PCR assay to identify the species of parasites (P. knowlesi, P. coatneyi, P. fieldi, P. cynomolgi, and P. inui) present. All the peridomestic macaques sampled were tested negative for malaria, while 80.5% of the 379 wild macaques were infected. All five simian Plasmodium species were detected; P. cynomolgi being the most prevalent (71.5%), followed by P. knowlesi (47.5%), P. inui (42.0%), P. fieldi (32.5%), and P. coatneyi (28.5%). Co-infection with multiple species of Plasmodium parasites was also observed. The study revealed that Singapore's wild long-tailed macaques are natural hosts of the five simian malaria parasite species, while no malaria was detected in all peridomestic macaques tested. Therefore, the risk of simian malaria transmission to the general human population is concluded to be low. However, this can be better demonstrated with the incrimination of the vectors of simian malaria parasites in Singapore.

Down-regulation of lysosomal protein ABCB6 increases gossypol susceptibility in Helicoverpa armigera.

Cotton bollworm (Helicoverpa armigera) is the major insect herbivore of cotton plants. As its larvae feed and grow on cotton, H. armigera can likely tolerate gossypol, the main defense metabolite produced by cotton plants, through detoxification and sequestration mechanisms. Recent reports have shown that various P450 monooxygenases and UDP-glycosyltransferases in H. armigera are involved in gossypol detoxification, while the roles of ABC transporters, another gene family widely associated with metabolite detoxification, remain to be elucidated. Here, we show that ingestion of gossypol-infused artificial diet and cotton leaves significantly induced the expression of HaABCB6 in H. armigera larvae. Knockdown and knockout of HaABCB6 increased sensitivity of H. armigera larvae to gossypol. Moreover, HaABCB6-GFP fusion protein was localized on lysosomes in Hi5 cells and its overexpression significantly enhanced gossypol tolerance in vitro. These experimental results strongly support that HaABCB6 plays an important role in gossypol detoxification by H. armigera.

Characteristics of vascular anastomoses in monochorionic twin 587 placentas with selective intrauterine growth restriction via 89 three-dimensional computed tomography angiography.

OBJECTIVE: To determine the characteristics of the choriovascular anatomy, especially the potential role of arteriovenous perfusion imbalance in the pathogenesis of selective intrauterine growth restriction (sIUGR) using three-dimensional computed tomography angiography (3D-CTA). METHOD: Computed tomography angiography of the placental choriovascular tree from 15 twins with sIUGR and 15 twins without sIUGR were analyzed, and inter-twin vascular anastomoses were compared between the placentas from these two groups. The parameters evaluated were the presence and measures of artery-to-artery anastomoses (AAA), vein-to-vein anastomoses (VVA) or artery-to-vein anastomoses (AVA). RESULTS: The frequency of AAA, VVA, and AVA did not differ significantly between sIUGR and without sIUGR-pairs. The area of the vein draining to the AVA in the larger twin's placenta was significantly greater in sIUGR compared to when no sIUGR was present. Based on the net cross-sectional area difference we speculate that in sIUGR there is net flow from the smaller to the larger twin. CONCLUSION: We used 3D-CTA to display the vascular anastomoses in sIUGR twin pairs, demonstrating a difference in cross-sectional diameter of the vein draining to the AVA.

Is waist circumference a negative predictor of calcaneal bone mineral density in adult Chinese men with normal weight?

BACKGROUND: Our study aimed to evaluate the association between waist circumference (WC) and calcaneal bone mineral density (BMD) in adult Chinese men with normal weight. METHODS: This was a cross-sectional study. A total of 4,663 male participants aged 40 years or older residing in Ningde and Wuyishan, two cities locating in Fujian province of China, were randomly recruited between 2011 and 2012. Each participant should complete a standard questionnaire, undergo anthropometric and calcaneus quantitative ultrasound (QUS) measurements and have blood sample taken. Anthropometric, biochemical and calcaneal QUS parameters of 1,583 male participants with BMI ranging from 18.5 to 22.9 were included in the analysis. WC was divided into quartiles (Q1-Q4: <71, 71-75, 75-78, >78 cm). The relationship between WC (quartiles) and BMD was analyzed by multiple linear regression models. RESULTS: Mean age of the whole population was 54.6±9.8 years. Anthropometric and biochemical parameters were almost normal. Multiple linear regression analysis showed that BMD was negatively associated with increasing WC quartiles except for Q2 after adjusting for age and BMI, and this relationship remained negative except for Q2 when further adjustment was made for other covariates. Multiple logistic regression model also showed that the risks of osteopenia and osteoporosis increased across WC quartiles. CONCLUSIONS: The present study indicated that WC was a negative predictor of calcaneal BMD in adult Chinese men with normal weight. It suggests that, even for the normal-weight Asian males, monitoring accrual of abdominal adipose is still helpful for the purpose of preventing bone loss.

EXPOSURE TO FAMINE IN EARLY LIFE AND THE RISK OF OSTEOPOROSIS IN ADULTHOOD: A PROSPECTIVE STUDY.

Objective: To assess the association between famine exposure in early life and osteoporosis in adulthood. Methods: A total of 2,292 participants born between 1955 and 1965 in Fujian Province were selected; after 3 years, 1,378 participants attended a follow-up research visit. Calcaneus bone mineral density and bone quality were measured by quantitative ultrasound. The T-score was used to assess bone mineral density, and the parameters quantitative ultrasound index (QUI), speed of sound (SOS), and broadband ultrasonic attenuation (BUA) were used to assess bone quality. A T-score threshold of -1.8 was defined as osteoporosis, and a possible vertebral fracture was considered as a prospective height loss of 0.8 inches or more. Results: Compared with the nonexposed cohort, risks of osteoporosis for fetal-, early childhood, and mid-childhood famine-exposed cohorts in postmenopausal women were adjusted odds ratio (OR), 3.741 (95% confidence interval [CI], 1.233, 11.44) versus OR 2.894 (95% CI, 0.997, 8.571) versus OR 4.699 (95% CI, 1.622, 13.612) by logistic regression but not significant in men. Moreover, the fetal-exposed cohort had a weak negative relation with QUI (ß, -5.07 [-10.226, 0.127]) and BUA (ß, -4.321 [-0.88, 0.238]). The early- and mid-childhood-exposed cohorts had significantly lower QUI (ß, -7.085 [-11.799, -2.372] versus ß, -10.845 [-15.68, -6.01]) and BUA (ß, -6.381 [-10.515, -2.246] versus ß, -8.573 [-12.815, -4.331]) than the nonexposed cohort by linear regression. None of the famine-exposed cohorts had a significant relationship with SOS. Conclusion: Famine exposure during early life is associated with higher risk of osteoporosis in adulthood, which is most obvious in postmenopausal women. Furthermore, famine exposure in early life has adverse effects on bone quality. Abbreviations: BMD = bone mineral density; BUA = broadband ultrasonic attenuation; CI = confidence interval; OR = odds ratio; QUI = quantitative ultrasound index; QUS = quantitative ultrasound; SOS = speed of sound.

Urban-rural inequalities in suicide among elderly people in China: a systematic review and meta-analysis.

BACKGROUND: China has an unusual pattern of suicides, with overall suicide rates in rural areas higher than urban areas. While suicide rates have decreased dramatically, older people increasingly contribute to the overall burden of suicide. However, it is unclear if elderly people within rural areas experience greater suicide risk than those in urban areas. We aimed to systematically review the incidence of suicide in rural and urban China among the elderly (aged over 60 years), with a view to describing the difference in rates between rural and urban areas and trends over time. METHODS: Chinese and English language articles were searched for using four databases: EMBASE (Ovid), MEDLINE (Ovid), PsycINFO (EBSCOhost) and CNKI (in Chinese). Articles describing completed suicide among elderly people in both rural and urban areas in mainland China were included. The adapted Newcastle-Ottawa Scale (NOS) was used to assess risk of bias. One reviewer (ML) assessed eligibility, performed data extraction and assessed risk of bias, with areas of uncertainty discussed with the second reviewer (SVK). Random effects meta-analysis was conducted. Suicide methods in different areas were narratively summarised. RESULTS: Out of a total 3065 hits, 24 articles were included and seven contributed data to meta-analysis. The sample size of included studies ranged from 895 to 323.8 million. The suicide rate in the general population of China has decreased in recent decades over previous urban and rural areas. Suicide rates amongst the elderly in rural areas are higher than those in urban areas (OR = 3.35; 95% CI of 2.48 to 4.51; I2 = 99.6%), but the latter have increased in recent years. Insecticide poisoning and hanging are the most common suicide methods in rural and urban areas respectively. Suicide rates for these two methods increase with age, being especially high in elderly people. CONCLUSIONS: The pattern of suicide in China has changed in recent years following urbanisation and aging. Differences in suicide rates amongst the elderly exist between rural and urban areas. Addressing the high suicide rate amongst the elderly in rural China requires a policy response, such as considering measures to restrict access to poisons.

Association Between Bone Mineral Density and Pancreatic ß-Cell Function in Elderly Men and Postmenopausal Women.

PURPOSE: To explore the association between bone mineral density (BMD) and ß-cell function. METHODS: A cross-sectional study was performed in Fujian, China, from 2011 to 2012. The study included 572 elderly men older than age 60 years and 1558 postmenopausal women aged 45 to 86 years, excluding those with diabetes and insulin resistance. Fasting glucose and insulin concentrations were measured. Pancreatic ß-cell function was estimated by using the homeostasis model assessment (HOMA-ß). Calcaneus BMD was measured by using quantitative ultrasonography. Multiple regression analyses were applied to explore the association. RESULTS: Participants with decreased BMD had lower fasting glucose (P < 0.001 in postmenopausal women; P = 0.007 in elderly men) and greater HOMA-ß (P = 0.001 in postmenopausal women; P = 0.008 in elderly men) than those with normal BMD, whereas no statistical differences in insulin were seen among categories of BMD. After adjustment for all confounders, HOMA-ß was still significantly negatively related to BMD in both groups (all P < 0.001), and remarkable positive relationships were found between BMD and fasting glucose. Furthermore, binary logistic regression presented fully adjusted odds ratios for diabetes in those with osteoporosis vs those with normal BMD: 0.60 [95% confidence interval (CI), 0.38 to 0.94] and 0.66 (95% CI, 0.49 to 0.91) in the original selected population of elderly men (n = 1070) and postmenopausal women (n = 2825), respectively. CONCLUSIONS: BMD was independently inversely associated with HOMA-ß and positively associated with fasting glucose in both elderly men and postmenopausal women, suggesting that bone mass may be a predictor of glucose metabolism. Further research is needed to verify the associations and determine the exact mechanism underlying them.

wMel limits zika and chikungunya virus infection in a Singapore Wolbachia-introgressed Ae. aegypti strain, wMel-Sg.

BACKGROUND: Zika (ZIKV) and Chikungunya (CHIKV) viruses are emerging Aedes-borne viruses that are spreading outside their known geographic range and causing wide-scale epidemics. It has been reported that these viruses can be transmitted efficiently by Ae. aegypti. Recent studies have shown that Ae. aegypti when transinfected with certain Wolbachia strains shows a reduced replication and dissemination of dengue (DENV), Chikungunya (CHIKV), and Yellow Fever (YFV) viruses. The aim of this study was to determine whether the wMel strain of Wolbachia introgressed onto a Singapore Ae. aegypti genetic background was able to limit ZIKV and CHIKV infection in the mosquito. METHODOLOGY/PRINCIPAL FINDINGS: Five to seven-day old mosquitoes either infected or uninfected with wMel Wolbachia were orally infected with a Ugandan strain of ZIKV and several outbreak strains of CHIKV. The midgut and salivary glands of each mosquito were sampled at days 6, 9 and 13 days post infectious blood meal to determine midgut infection and salivary glands dissemination rates, respectively. In general, all wild type Ae. aegypti were found to have high ZIKV and CHIKV infections in their midguts and salivary glands, across all sampling days, compared to Wolbachia infected counterparts. Median viral titre for all viruses in Wolbachia infected mosquitoes were significantly lower across all time points when compared to wild type mosquitoes. Most significantly, all but two and one of the wMel infected mosquitoes had no detectable ZIKV and CHIKV, respectively, in their salivary glands at 14 days post-infectious blood meal. CONCLUSIONS: Our results showed that wMel limits both ZIKV and CHIKV infection when introgressed into a Singapore Ae. aegypti genetic background. These results also strongly suggest that female Aedes aegypti carrying Wolbachia will have a reduced capacity to transmit ZIKV and CHIKV.

Placental characteristics in monochorionic twins with selective intrauterine growth restriction assessed by gradient angiography and three-dimensional reconstruction.

OBJECTIVE: To investigate the placental characteristics in selective intrauterine growth restriction (sIUGR) using gradient angiography and three-dimensional (3D) reconstruction from computed tomography (CT) scan data. METHODS: This study included 23 sIUGR cases and 16 monochorionic twin-pregnancies without sIUGR. We injected nonionic iodinated contrast agents into the umbilical arteries and veins. Placental characteristics were analyzed after CT scanning and 3D reconstruction. RESULTS: 73.9% of smaller twins in sIUGR cases had marginal or velamentous cord insertions and less placental sharing. The terminal branch of the arterial tree was scored III-IV in smaller sIUGR twins, while it was scored V-VII in normal monochorionic twins and larger sIUGR twins. Arterio-arterial (A-A) anastomoses presented in all monochorionic placentas. Veno-venous (V-V) anastomoses present in 83.3% (5/6) of Type III sIUGR cases, which was higher than observed in Type I-II cases. The mean diameters of A-A and V-V anastomoses were larger in Type III sIUGR cases. CONCLUSIONS: Gradient angiography and 3D placental models displayed different placental angioarchitectures and voluminal placental sharing among three types of sIUGR cases. Placental dysplasia in the smaller twin may cause abnormal cord insertion and unequal placental sharing. The inter-twin anatomoses influence the umbilical cord artery (UA) Doppler and natural pathogenesis of sIUGR.

Diagnostic challenges and case management of the first imported case of Plasmodium knowlesi in Sri Lanka.

BACKGROUND: Sri Lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. Imported malaria remains a challenge to resurgence of the disease. The diagnostic challenges encountered and the rapid response initiated to manage a Plasmodium infection, which was later confirmed as Plasmodium knowlesi, the first reported case from Sri Lanka, is discussed. CASE PRESENTATION: An army officer who returned from Malaysia in October 2016 was found to be positive for Plasmodium both by microscopy and rapid diagnostic test (RDT) by the Anti Malaria Campaign Sri Lanka (AMC) during his third visit to a health care provider. Microscopy findings were suspicious of P. knowlesi infection as the smears showed parasite stages similar to both Plasmodium malariae and Plasmodium falciparum. Nested PCR at AMC confirmed Plasmodium genus, but not the species. In the absence of species confirmation, the patient was treated as a case of P. falciparum. The presence of P. knowlesi was later confirmed by a semi-nested PCR assay performed at the Environmental Health Institute, National Environmental Agency in Singapore. The parasite strain was also characterized by sequencing the circumsporozoite gene. Extensive case investigation including parasitological and entomological surveillance was carried out. CONCLUSIONS: Plasmodium knowlesi should be suspected in patients returning from countries in the South Asian region where the parasite is prevalent and when blood smear results are inconclusive.

Is Retinal Microvascular Abnormalities an Independent Risk Factor of Vertebral Fractures? A Prospective Study From a Chinese Population.

Low bone mineral density (BMD) and microvascular diseases (MVD) share various common risk factors; however, whether MVD is an independent risk factor of vertebral fractures is incompletely understood. The aim of this study is to clarify whether MVD is an independent risk factor of vertebral fractures. In this prospective study, calcaneal BMD and retinal microvascular abnormalities were assessed at baseline from June 2011 to January 2012. A total of 2176 premenopausal women, 2633 postmenopausal women, 2998 men aged <65 years, and 737 men aged ≥65 were included. Then with/without retinal microvascular abnormalities cohorts were followed for an average of 2.93 years to find out the relationship between MVD and vertebral fractures. At the baseline, after full adjustment, retinal microvascular abnormalities were related to risk of low BMD only in men aged ≥65 years (odds ratio [OR] = 2.506; 95% confidence interval [CI] 1.454-4.321; p = 0.001). After follow-up of 2.93 years, retinal microvascular abnormalities were related to risk of vertebral fractures in men aged ≥65 years (OR = 2.475; 95% CI 1.085-5.646; p = 0.031) when adjustment for confounding factors. However, no associations were found between MVD and vertebral fractures in men aged <65 years, premenopausal women, and postmenopausal women. When stratified by diabetes, in the without-diabetes group, the men with retinal microvascular abnormalities had higher risk for vertebral fractures than without retinopathy (OR = 2.194; 95% CI 1.097-4.389; p = 0.026); however, the difference was not found in women. In the diabetes group, there were no significant differences of risk for vertebral fractures between those with retinal microvascular abnormalities and those without both in men and women. Stratified by hypertension, the men with retinopathy had higher risk for vertebral fractures than those without among the hypertension group (OR = 2.034; 95% CI 1.163-3.559; p = 0.013), but a difference was not found among women. In the without-hypertension group, no relation was found between MVD and fracture both in men and women. In conclusion, MVD is an independent risk factor of vertebral fractures in old men. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Evaluation of the sacral nerve plexus in pelvic endometriosis by three-dimensional MR neurography.

PURPOSE: To investigate the feasibility of three-dimensional MR neurography (3D MRN) for the sacral plexus using sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences, and to demonstrate structural abnormalities in the pelvic nerve of women with pelvic endometriosis. MATERIALS AND METHODS: Twenty patients with pelvic endometriosis and 20 healthy controls were examined by contrast-enhanced 3D short time inversion recovery T2-weighted imaging (CE 3D STIR T2WI) SPACE sequences on 3 Tesla MRI. Image quality and diagnostic confidence of the sequences in identifying abnormalities of the sacral plexus were analyzed and compared with conventional three-plane images of 2D turbo-spin echo T2-weighted images (2D TSE T2WI). The changes in the sacral plexus caused by endometrial lesions were evaluated. RESULTS: The sacral plexus was clearly revealed in both healthy controls and patients with endometriosis on 3D STIR SPACE images. A good agreement was reached in the evaluation of both imaging quality (Kappa value [κ] = 0.73-1.00) and diagnostic confidence (κ = 0.66-0.81) when compared between the two independent readers. Abnormalities caused by endometriosis were identified in 17 patients, unilaterally in 10 patients, and bilaterally in 7 patients. Nerve fiber abnormalities of lumbar 5 (L5) were detected in 11 patients, of sacral 1 (S1) in 14 patients and of sacral 2 (S2) in 9 patients. CONCLUSION: CE 3D STIR SPACE sequences demonstrate its significant capacity to investigate and map the sacral plexus, and reveal the compression and adhesion of the sacral plexus nerve as a result of ectopic lesions. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:1225-1231.