Deep Brain Stimulation-Induced Transient Effects in the Habenula

The habenula, located in the epithalamus, has been implicated in various psychiatric disorders including mood disorders and schizophrenia. This study explored the transient effects of deep brain stimulation in the habenula. Each of the four patients (two with bipolar disorder and two with schizophrenia) was tested with eight deep brain stimulation contacts. Patients were examined via transient electrical stimulation 1 month after deep brain stimulation surgery. The pulse width was 60 μs and the voltage ranged from 0 V to a maximum of 10 V, increasing in increments of 1 V. Each patient received stimulation at two frequencies, 60 and 135 Hz. A total of 221 out of 385 active trials elicited stimulation-induced effects. The three most common transient effects were numbness, heart rate changes, and pain. The incidence of numbness, heart rate changes, pain, and involuntary movements increased with the increase in stimulation voltage. Through contralateral stimulation, numbness was triggered in all parts of the body except the scalp. The obtained stimulus-response maps suggested a possible somatosensory organization of the habenula

An International Survey of Deep Brain Stimulation Utilization in Asia and Oceania: The DBS Think Tank East.

Introduction: To evaluate the current utilization and challenges in fully implementing the use of deep brain stimulation (DBS) treatment in Asia and Oceania. Methods: We conducted a medical literature search to identify DBS research performed by investigators with a primary affiliation in Asian and Oceania countries between March 1, 2013, and March 1, 2019, followed by an international survey-based study. Additionally, we obtained added information regarding the DBS challenges and opportunities from the technology/industry perspective within China and Japan. We also described the current situation of DBS in India. Results: Most publications (390/494; 78.95%) in the English language originated from East Asia. In West Asia, Turkey, Israel, and Iran accounted for most DBS publications. We found no publications from the remaining 35 Asian countries. Lack of community referrals to tertiary centers was identified as the most common limitation for the widespread use of DBS in Asia (68.97%). In China, despite an increasing number of centers performing DBS surgeries, most of them accomplished less than 10 cases per year. In contrast, the number of DBS cases in Japan has been decreasing. Centers offering DBS surgeries as well as corresponding fellowship training in India are limited. Conclusion: Appropriate referrals, access, infrastructure, and the presence of full multidisciplinary DBS teams are common limitations of DBS in Asia. Most centers in China, Japan, and India performed less than 10 cases per year and a future study is expected to address the impact on quality in centers performing such few cases

Smart Bacteria-Responsive Drug Delivery Systems in Medical Implants

With the rapid development of implantable biomaterials, the rising risk of bacterial infections has drawn widespread concern. Due to the high recurrence rate of bacterial infections and the issue of antibiotic resistance, the common treatments of peri-implant infections cannot meet the demand. In this context, stimuli-responsive biomaterials have attracted attention because of their great potential to spontaneously modulate the drug releasing rate. Numerous smart bacteria-responsive drug delivery systems (DDSs) have, therefore, been designed to temporally and spatially release antibacterial agents from the implants in an autonomous manner at the infected sites. In this review, we summarized recent advances in bacteria-responsive DDSs used for combating bacterial infections, mainly according to the different trigger modes, including physical stimuli-responsive, virulence-factor-responsive, host-immune-response responsive and their combinations. It is believed that the smart bacteria-responsive DDSs will become the next generation of mainstream antibacterial therapies

Diagnostic Accuracy of Procalcitonin Compared to C-Reactive Protein and Interleukin 6 in Recognizing Gram-Negative Bloodstream Infection: A Meta-Analytic Study

Objective. Gram-negative bloodstream infections (GNBSIs), especially those caused by antibiotic-resistant species, have become a public health challenge. Procalcitonin (PCT) showed promising potential in early diagnosis of GNBSI; however, little was known about its performance under different clinical settings. We here systematically assessed the diagnostic accuracy of PCT in recognizing GNBSI and made direct comparisons with C-reactive protein (CRP) and interleukin 6 (IL-6). Methods. PubMed, Embase, ISI Web of Knowledge, and Scopus were searched from inception to March 15th, 2019. Area under the summary receiver operating characteristic curve (AUC), pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. Hierarchical summary receiver operating characteristic (HSROC) model was used for the investigation of heterogeneity and for comparisons between markers. Results. 25 studies incorporating 50933 suspected BSI episodes were included. Pooled sensitivity and specificity for PCT were 0.71 and 0.76, respectively. The overall AUC was 0.80. The lowest AUCs were found in patients with febrile neutropenia (0.69) and hematological malignancy (0.69). The highest AUC was found in groups using electrochemiluminescence immunoassay (0.87). In direct comparisons, PCT showed better overall performance than CRP with the AUC being 0.85 (95% CI 0.81–0.87) for PCT and 0.78 (95% CI 0.74–0.81) for CRP, but the relative DORs varied with thresholds between PCT and CRP (p<0.001). No significant difference was found either in threshold (p=0.654) or in accuracy (p=0.480) between PCT and IL-6 in diagnosing GNBSI. Conclusions. PCT was helpful in recognizing GNBSI, but the test results should be interpreted carefully with knowledge of patients’ medical condition and should not serve as the only criterion for GNBSI. Further prospective studies are warranted for comparisons between different clinical settings

Approximate unconditional test procedure for comparing two ordered multinomials

The asymptotic and exact conditional methods are widely used to compare two ordered multinomials. The asymptotic method is well known for its good performance when the sample size is sufficiently large. However, Brown et al. (2001) gave a contrary example in which this method performed liberally even when the sample size was large. In practice, when the sample size is moderate, the exact conditional method is a good alternative, but it is often criticised for its conservativeness. Exact unconditional methods are less conservative, but their computational burden usually renders them infeasible in practical applications. To address these issues, we develop an approximate unconditional method in this paper. Its computational burden is successfully alleviated by using an algorithm that is based on polynomial multiplication. Moreover, the proposed method not only corrects the conservativeness of the exact conditional method, but also produces a satisfactory type I error rate. We demonstrate the practicality and applicability of this proposed procedure with two real examples, and simulation studies are conducted to assess its performance. The results of these simulation studies suggest that the proposed procedure outperforms the existing procedures in terms of the type I error rate and power, and is a reliable and attractive method for comparing two ordered multinomials.Asymptotic test Exact conditional test Exact unconditional test Approximate unconditional test Wilcoxon statistic Two ordered Multinomials

Structural and functional correlates of the response to deep brain stimulation at ventral capsule/ventral striatum region for treatment-resistant depression.

Peer reviewed: TrueAcknowledgements: We thank Dr Lifu Deng and Dr. Tianzhu Xiong for valuable advice on imaging data processing.BACKGROUND: Though deep brain stimulation (DBS) shows increasing potential in treatment-resistant depression (TRD), the underlying neural mechanisms remain unclear. Here, we investigated functional and structural connectivities related to and predictive of clinical effectiveness of DBS at ventral capsule/ventral striatum region for TRD. METHODS: Stimulation effects of 71 stimulation settings in 10 TRD patients were assessed. The electric fields were estimated and combined with normative functional and structural connectomes to identify connections as well as fibre tracts beneficial for outcome. We calculated stimulation-dependent optimal connectivity and constructed models to predict outcome. Leave-one-out cross-validation was used to validate the prediction value. RESULTS: Successful prediction of antidepressant effectiveness in out-of-sample patients was achieved by the optimal connectivity profiles constructed with both the functional connectivity (R=0.49 at p<10-4; deviated by 14.4±10.9% from actual, p<0.001) and structural connectivity (R=0.51 at p<10-5; deviated by 15.2±11.5% from actual, p<10-5). Frontothalamic pathways and cortical projections were delineated for optimal clinical outcome. Similarity estimates between optimal connectivity profile from one modality (functional/structural) and individual brain connectivity in the other modality (structural/functional) significantly cross-predicted the outcome of DBS. The optimal structural and functional connectivity mainly converged at the ventral and dorsal lateral prefrontal cortex and orbitofrontal cortex. CONCLUSIONS: Connectivity profiles and fibre tracts following frontothalamic streamlines appear to predict outcome of DBS for TRD. The findings shed light on the neural pathways in depression and may be used to guide both presurgical planning and postsurgical programming after further validation