The Influence of Etiology and Stimulation Target on the Outcome of Deep Brain Stimulation for Chronic Neuropathic Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Deep brain stimulation (DBS) to treat chronic neuropathic pain has shown variable outcomes. Variations in pain etiologies and DBS targets are considered the main contributing factors, which are, however, underexplored owing to a paucity of patient data in individual studies. An updated meta-analysis to quantitatively assess the influence of these factors on the outcome of DBS for chronic neuropathic pain is warranted, especially considering that the anterior cingulate cortex (ACC) has emerged recently as a new DBS target. MATERIALS AND METHODS: A comprehensive literature review was performed in PubMed, Embase, and Cochrane data bases to identify studies reporting quantitative outcomes of DBS for chronic neuropathic pain. Pain and quality of life (QoL) outcomes, grouped by etiology and DBS target, were extracted and analyzed (α = 0.05). RESULTS: Twenty-five studies were included for analysis. Patients with peripheral neuropathic pain (PNP) had a significantly greater initial stimulation success rate than did patients with central neuropathic pain (CNP). Both patients with CNP and patients with PNP with definitive implant, regardless of targets, gained significant follow-up pain reduction. Patients with PNP had greater long-term pain relief than did patients with CNP. Patients with CNP with ACC DBS gained less long-term pain relief than did those with conventional targets. Significant short-term QoL improvement was reported in selected patients with CNP after ACC DBS. However, selective reporting bias was expected, and the improvement decreased in the long term. CONCLUSIONS: Although DBS to treat chronic neuropathic pain is generally effective, patients with PNP are the preferred population over patients with CNP. Current data suggest that ACC DBS deserves further investigation as a potential way to treat the affective component of chronic neuropathic pain.

Effects of lactic acid bacteria fermentation on the physicochemical and structural characteristics of starch in blends of glutinous and japonica rice.

In this study, the effects of lactic acid bacteria (LAB) fermentation on the physicochemical and structural characteristics of mixed starches in blends of glutinous and japonica rice were investigated. Five starter cultures improved in varying degrees the hydration ability, transparency, and freeze-thaw stability of the mixed starches. Mixed starch I, prepared by fermentation of Lactobacillus acidophilus HSP001, exhibited optimal water-holding capacity, solubility, and swelling power. In comparison, mixed starches V and III involved fermentation of L. acidophilus HSP001 and Latilactobacillus sakei HSP002, using ratios of 2:1 and 1:1 to achieve higher transparency and freeze-thaw stability, respectively. The LAB-fermented, mixed starches exhibited excellent pasting properties due to their high peak viscosities and low setback values. Moreover, the viscoelasticity of mixed starches III-V, prepared by compound fermentation of L. acidophilus HSP001 and L. sakei HSP002 in ratios of 1:1, 1:2, and 2:1, respectively, proved superior to their single strain fermentation counterparts. Meanwhile, LAB fermentation resulted in reduced gelatinization enthalpy, relative crystallinity, and short-range ordered degree. Thus, the effects of five LAB starter cultures on mixed starches were inconsistent, but these results provide a theoretical basis for the application of mixed starches. PRACTICAL APPLICATION: Lactic acid bacteria was used to ferment blends of glutinous and japonica rice. Fermented mixed starch had better hydration, transparency, and freeze-thaw stability. Fermented mixed starch exhibited nice pasting properties and viscoelasticity. LAB fermentation corroded starch granules, leading to the decrease of ΔH. Relative crystallinity and short-range order of fermented mixed starch decreased.

Inhibitory effect and mechanism of a compound essential oils on Cladophora glomerata.

Cladophora glomerata (C. glomerata) is a typical macroalgae inducing green tide and affecting economic benefits in aquaculture. A high-efficiency, environment friendly compound essential oils (CEOs) was provided to control C. glomerata blooms. The inhibition effect of CEOs against C. glomerata was assessed through the growth, cellular morphology and the physiological and biochemical indexes of C. glomerata. Results of the Chl-a content indicated that 300 µL/L CEOs could significantly inhibited the growth (85 % ± 2 %) of C. glomerata on the 11th day; the damage degree of algal thallus can be observed based on the results of cell morphology; the results of the physiological and biochemical indicators presented the decreased photosynthetic capacity, the dysfunction of antioxidant system and the algal apoptosis gene caspase- 8, 9, 3 activated when C. glomerata exposed to CEOs. This study elucidated the effect and mechanism of CEOs control the green tide induced by C. glomerata.

The Caulobacter crescentus DciA promotes chromosome replication through topological loading of the DnaB replicative helicase at replication forks.

The replicative DNA helicase translocates on single-stranded DNA to drive replication forks during chromosome replication. In most bacteria the ubiquitous replicative helicase, DnaB, co-evolved with the accessory subunit DciA, but how they function remains incompletely understood. Here, using the model bacterium Caulobacter crescentus, we demonstrate that DciA plays a prominent role in DNA replication fork maintenance. Cell cycle analyses using a synchronized Caulobacter cell population showed that cells devoid of DciA exhibit a severe delay in fork progression. Biochemical characterization revealed that the DnaB helicase in its default state forms a hexamer that inhibits self-loading onto single-stranded DNA. We found that upon binding to DciA, the DnaB hexamer undergoes conformational changes required for encircling single-stranded DNA, thereby establishing the replication fork. Further investigation of the functional structure of DciA revealed that the C-terminus of DciA includes conserved leucine residues responsible for DnaB binding and is essential for DciA in vivo functions. We propose that DciA stimulates loading of DnaB onto single strands through topological isomerization of the DnaB structure, thereby ensuring fork progression. Given that the DnaB-DciA modules are widespread among eubacterial species, our findings suggest that a common mechanism underlies chromosome replication.

Large-Scale Preparation of Uniform Millet Bread-like Durable Benzoxazine-Phthalonitrile Foam with Outstanding Mechanical and Thermal Properties.

It is essentially important to develop durable polymer foams for services in high-temperature conditions. The current study reported the preparations and properties of a high-performance benzoxazine-phthalonitrile (BZPN) foam by utilizing azodicarbonamide and tween-80 as the blowing agent and stabilizer, respectively. Rheological and curing studies indicated that the appropriate foaming temperature for BZPN foam is below 180 °C, and its foaming viscosity window is below 20 Pa·s. Guided by these results, uniform millet bread-like BZPN foams with decimeter leveling size were successfully realized, suggesting the high prospect of large-scale production. The structural, mechanical, and thermal properties of BZPN foams were then investigated in detail. BZPN foam involves a hierarchical fracture mechanism during the compressive test, and it shows a high compression strength of over 6 MPa. During a burning test over 380 °C, no visible smoke, softening, or droplet phenomena appeared and the macroscopic structure of BZPN foam was well maintained. Mechanically robust, flame-retardant, and uniform large-size BZPN foam are promising light durable materials with high service temperatures, i.e., as filling materials even in a very narrow pipette.

Algicidal Effects of a High-Efficiency Algicidal Bacterium Shewanella Y1 on the Toxic Bloom-Causing Dinoflagellate Alexandrium pacificum.

Alexandriumpacificum is a typical toxic bloom-forming dinoflagellate, causing serious damage to aquatic ecosystems and human health. Many bacteria have been isolated, having algicidal effects on harmful algal species, while few algicidal bacteria have been found to be able to lyse A. pacificum. Herein, an algicidal bacterium, Shewanella Y1, with algicidal activity to the toxic dinoflagellate A. pacificum, was isolated from Jiaozhou Bay, China, and the physiological responses to oxidative stress in A. pacificum were further investigated to elucidate the mechanism involved in Shewanella Y1. Y1 exhibited a significant algicidal effect (86.64 ± 5.04% at 24 h) and algicidal activity in an indirect manner. The significant declines of the maximal photosynthetic efficiency (Fv/Fm), initial slope of the light limited region (alpha), and maximum relative photosynthetic electron transfer rate (rETRmax) indicated that the Y1 filtrate inhibited photosynthetic activities of A. pacificum. Impaired photosynthesis induced the overproduction of reactive oxygen species (ROS) and caused strong oxidative damage in A. pacificum, ultimately inducing cell death. These findings provide a better understanding of the biological basis of complex algicidal bacterium-harmful algae interactions, providing a potential source of bacterial agent to control harmful algal blooms.

Hyperdirect connectivity of opercular speech network to the subthalamic nucleus.

How the basal ganglia participate in the uniquely human behavior of speech is poorly understood, despite their known role in modulating critical aspects of cognitive and motor behavior. The subthalamic nucleus (STN) is well positioned to facilitate basal ganglia functions critical for speech. Using electrocorticography in patients undergoing awake deep brain stimulation (DBS) surgery, evidence is reported for a left opercular hyperdirect pathway in humans via stimulating the STN and examining antidromic-evoked activity in the left temporal, parietal, and frontal opercular cortex. These high-resolution cortical and subcortical mapping data provide evidence for hyperdirect connectivity between the inferior frontal gyrus and the STN. In addition, evoked potential data are consistent with the presence of monosynaptic projections from areas of the opercular speech cortex that are primarily sensory, including the auditory cortex, to the STN. These connections may be unique to humans, evolving alongside the ability for speech.

Lateralized and Region-Specific Thalamic Processing of Lexical Status during Reading Aloud.

To explore whether the thalamus participates in lexical status (word vs nonword) processing during spoken word production, we recorded local field potentials from the ventral lateral thalamus in 11 essential tremor patients (three females) undergoing thalamic deep-brain stimulation lead implantation during a visually cued word and nonword reading-aloud task. We observed task-related beta (12-30 Hz) activity decreases that were preferentially time locked to stimulus presentation, and broadband gamma (70-150 Hz) activity increases, which are thought to index increased multiunit spiking activity, occurring shortly before and predominantly time locked to speech onset. We further found that thalamic beta activity decreases bilaterally were greater when nonwords were read, demonstrating bilateral sensitivity to lexical status that likely reflects the tracking of task effort; in contrast, greater nonword-related increases in broadband gamma activity were observed only on the left, demonstrating lateralization of thalamic broadband gamma selectivity for lexical status. In addition, this lateralized lexicality effect on broadband gamma activity was strongest in more anterior thalamic locations, regions which are more likely to receive basal ganglia than cerebellar afferents and have extensive connections with prefrontal cortex including Brodmann's areas 44 and 45, regions consistently associated with grapheme-to-phoneme conversions. These results demonstrate active thalamic participation in reading aloud and provide direct evidence from intracranial thalamic recordings for the lateralization and topography of subcortical lexical status processing.SIGNIFICANCE STATEMENT Despite the corticocentric focus of most experimental work and accompanying models, there is increasing recognition of the role of subcortical structures in speech and language. Using local field potential recordings in neurosurgical patients, we demonstrated that the thalamus participates in lexical status (word vs nonword) processing during spoken word production, in a lateralized and region-specific manner. These results provide direct evidence from intracranial thalamic recordings for the lateralization and topography of subcortical lexical status processing.

Lateralized Effect of Thalamic Deep Brain Stimulation Location on Verbal Abstraction.

BACKGROUND: Regionalized thalamic activity has been implicated in language function, and yet the effect of thalamic deep brain stimulation (DBS) on language-related clinical outcomes is underexplored. OBJECTIVE: The objective of this study was to determine if the location of stimulation within the thalamus correlates with changes in language-related neuropsychological outcomes following DBS for essential tremor. METHODS: Thirty patients with essential tremor underwent comprehensive neuropsychological evaluations before and after DBS surgery targeting the ventral intermediate nucleus of the thalamus. Changes in neuropsychological functions were evaluated. The relationships between language-related outcomes and stimulation location were assessed using both categorical and linear methods. Any significant results were further validated using linear discriminant analysis. RESULTS: Most neuropsychological functions remained unchanged at the group level. However, outcome on a measure of verbal abstraction was significantly dependent on stimulation location along the anterior-posterior axis within the left ventral lateral thalamus, with anterior stimulation associated with reduced verbal abstraction performance. This result was supported by linear discriminant analysis, which showed that stimulation locations with improved and reduced verbal abstraction function were best separated by a vector nearly parallel to the anterior-posterior axis. No stimulation location dependence was found for verbal abstraction outcome in the right thalamus or for outcomes of other language functions in either hemisphere. CONCLUSION: We demonstrate an effect of thalamic DBS on verbal abstraction as a function of left thalamic topography. This finding provides clinical evidence for the lateralization and regionalization of thalamic language function that may be relevant for understanding nonmotor effects of stimulation. © 2021 International Parkinson and Movement Disorder Society.

The Use of Remote Programming for Spinal Cord Stimulation for Patients With Chronic Pain During the COVID-19 Outbreak in China.

OBJECTIVES: Due to the impact of COVID-19 epidemic, face-to-face follow-up treatments for patients with chronic pain and implanted spinal cord stimulation (SCS) devices are forced to be delayed or stopped. This has led to more follow ups being done remotely. Meanwhile, with the development of 4G/5G networks, smartphones, and novel devices, remote programming has become possible. Here, we investigated the demand and utility of remote follow-ups including remote programming for SCS for patients with chronic pain. MATERIALS AND METHODS: A questionnaire including questions on demographic characteristics, pain history, postimplantation life quality, standard follow-up experience, remote follow-up, and remote programming experience was sent to patients diagnosed as chronic intractable pain and treated with SCS during January 2019 to January 2020. RESULTS: A total of 64 participants completed the questionnaire. About 70% of participants expressed demands for remote follow-ups due to the inconvenience, high costs, and time consumption of traditional follow-up visits. Nearly 97% of participants have attempted remote follow-ups, and about 81% of participants have further tried remote programming. Approximately, 96% of them recognized the benefits. CONCLUSIONS: The remote programming was in high demand among participants. Most of the participants have tried remote follow-ups or even remote programming. The remote programming appeared to be more efficient, economic and were widely recognized among participants.

Subthalamic Nucleus and Sensorimotor Cortex Activity During Speech Production.

The sensorimotor cortex is somatotopically organized to represent the vocal tract articulators such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed LFP recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 human subjects (1 female) with Parkinson's disease during implantation of deep-brain stimulation (DBS) electrodes while they read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high-gamma (60-150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulators involved in the production of the initial consonants were topographically represented by high-gamma activity. We found that STN high-gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high-gamma activity varied along the ventral-dorsal trajectory of the electrodes, with greater high-gamma power recorded in the dorsal locations of the STN. Interestingly, the majority of significant articulator-discriminative activity in the STN occurred before that in sensorimotor cortex. These results demonstrate that articulator-specific speech information is contained within high-gamma activity of the STN, but with different spatial and temporal organization compared with similar information encoded in the sensorimotor cortex.SIGNIFICANCE STATEMENT Clinical and electrophysiological evidence suggest that the subthalamic nucleus (STN) is involved in speech; however, this important basal ganglia node is ignored in current models of speech production. We previously showed that STN neurons differentially encode early and late aspects of speech production, but no previous studies have examined subthalamic functional organization for speech articulators. Using simultaneous LFP recordings from the sensorimotor cortex and the STN in patients with Parkinson's disease undergoing deep-brain stimulation surgery, we discovered that STN high-gamma activity tracks speech production at the level of vocal tract articulators before the onset of vocalization and often before related cortical encoding.

[Chemical Constituents from Cynanchum paniculatum].

OBJECTIVE: To investigate the chemical constituents from Gynanchum paniculatum. METHODS: The constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography, and preparative TLC. Their structures were identified on the basis of spectral data and physiochemical characteristics. RESULTS: 15 compounds were isolated from 70% ethanol extract and identified as ß-sitosterol(1), ß-daucosterin (2), mudanoside A (3), paeonolide (4), santamarin (5), paeonol(6), annobraine (7), laricircsinol (8), α-asarone(9), 7-angelyheliotridine(10), ß-amyrin(11), uridine(12), kaempferol-3-O-ß-D-glucopyranosyl(1→2)α-L-arabinopyranoside(13), kaempferol-7-O-(4", 6"-di-p-hydroxycinnamoyl-2", 3"-diacetyl)-ß-D-glucopyranoside(14), and (2S, E)-N-[2-hydroxy-2-(4-hydroxyphenyl) ethyl] ferulamide (15). CONCLUSION: Compounds 4, 6, 8, 11, 12 and 15 are isolated from this plant for the first time, compounds 5 and 14 are firstly isolated from the palnts of Cynanchum genus.

Pre-existing mutations in reverse transcriptase of hepatitis B virus in treatment-naive Chinese patients with chronic hepatitis B.

High rate of viral replication and lacking of proofreading activity in hepatitis B virus (HBV) polymerase lead to the generation of mutations in HBV virus. Mutations in the reverse transcriptase (RT) region of HBV polymerase are demonstrated to be strongly associated with drug resistance during antiviral treatment. However, the presence of mutations as well as its clinical significance in treatment-naïve hepatitis patients (defined as pre-existing mutations) need to be further investigated. In the present study, a total of 168 serum samples from treatment-naive chronic hepatitis B (CHB) patients were collected, and the RT region of HBV polymerase was sequenced. The results showed that pre-existing mutations in the RT region of HBV polymerase were detected in 43 of 168 (25.6%) treatment-naive CHB patients within which there were no well-characterized primary nucleotide analogs (NAs) resistance sites. Three dominant sites at rt191, rt207 and rt226 were found mutant in 7(16.28%), 8(18.60%), and 14(32.56%) samples respectively among these 43 patients. No significant correlation was found between pre-existing mutations and gender, age, HBV genotype, ALT, HBeAg or HBV DNA loads. However, patients with pre-existing RT mutations under HBeAg sero-negative status exhibited decreased HBV DNA loads, which contributed to the decreased HBV DNA loads in the total HBeAg sero-negative patients. The above investigation indicated that there was a prevalence of pre-existing mutations in RT region of HBV polymerase which might affect the serum HBV DNA level in treatment-naive CHB patients. Its effects on the occurrence of NAs resistance and the prognosis after treatment need to be further investigated.

A high-affinity CDR-grafted antibody against influenza A H5N1 viruses recognizes a conserved epitope of H5 hemagglutinin.

Highly pathogenic avian influenza (HPAI) H5N1 virus infection is still a potential threat to public health worldwide. While vaccines and antiviral drugs are currently under development, neutralizing antibodies could offer an alternative strategy to prevent and treat H5N1 virus infection. In the present study, we had developed a humanized antibody against H5N1 viruses from mouse-derived hybridoma in order to minimize its immunogenicity for potential clinical application. The humanized antibody hH5M9 was generated by transferring the mouse complementarity determining region (CDR) residues together with four key framework region (FR) residues onto the FR of the human antibody. This humanized antibody exhibited high affinity and specificity comparable to the parental mouse or chimeric counterpart with broad and strong neutralization activity against all H5N1 clades and subclades except for Egypt clades investigated. Furthermore, through epitope mapping we identified a linear epitope on the top region of hemagglutinin (HA) that was H5N1 specific and conserved. Our results for the first time reported a humanized antibody against H5N1 viruses by CDR grafting method. With the expected lower immunogenicity, this humanized antibody was expected to be more efficacious than murine or human-mouse chimeric antibodies for future application in humans.

Prostaglandin E synthase is regulated in postnatal mouse testis.

Prostaglandins have important roles in the male reproductive system. In this study, we report on the distribution and regulation of cPGES during postnatal development of mouse testis. The expression of cPGES was weak in testis 5 days after birth and increased through the 10th and 15th day. From the 20th day onward, the cPGES expression in testis reached the level of adult mice. cPGES was expressed at a constantly low level in Sertoli cells in the testis from infant to adult stages. With the occurrence of meiosis during puberty, a high level of cPGES was detected in the spermatocytes and round spermatids, which was then maintained throughout the adulthood. In addition, cPGES was found highly expressed in the epididymis, seminal vesicles and vas deferens This suggests that cPGES in Sertoli cells in infant to juvenile mouse testis contributes to a basic PGE2 synthesis in seminiferous tubules. However, the high level of cPGES in spermatocytes and spermatids may maintain a high amount of PGE2 in seminiferous tubules, which may be tightly coupled with the spermatogenic cycle.

[Comparison of transurethral detaching resection and plasmakinetic transurethral resection of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To compare the clinical effects of transurethral detaching resection (TUDRP) and plasmakinetic transurethral resection of the prostate (PKRP) for benign prostatic hyperplasia (BPH). METHODS: We collected by the single blind method the clinical data of 81 cases of BPH treated by PKRP (n=41) and TUDRP (n=40), and compared the two groups of patients in their age, preoperative prostate volume, weight of the resected gland, operation time, intraoperative bleeding, time of postoperative Foley's catheter retention, and pre- and post-operative IPSS. RESULTS: The post-operative IPSS was significantly higher in the PKRP than in the TUDRP group (9.95 +/- 1.54 vs. 8.70 +/- 1.13, t = 0.0029, P = 0.0059). CONCLUSION: TUDPR has a better clinical effect than PKRP in the treatment of BPH.