Functional brain network analysis using electroencephalography in late-onset Lennox-Gastaut syndrome.

OBJECTIVE: We aimed to explore the clinical characteristics and functional network properties of patients with late-onset Lennox-Gastaut syndrome (LGS). METHODS: Late-onset LGS was defined by the appearance of LGS features after 8 years of age. We reviewed the medical charts of 9 patients with late-onset LGS, and performed electroencephalography connectivity analysis using graph theory. We assessed the clustering coefficient (CC) and characteristic path length (CPL), which are common basic measures of functional networks that represent local segregation and global integration. The characteristics and brain parameters of late-onset LGS were compared with a typical age-onset LGS group. RESULTS: Late onset LGS subjects were older than typical age onset LGS at the time of testing, but otherwise there were no significant differences in clinical characteristics. The late-onset group showed higher median CC values in the alpha (p = 0.045) and beta (p < 0.001) bands over brain regions implicated in cognitive processing. There were no significant differences in CPL between the LGS groups. CONCLUSIONS: Higher clustering coefficient values, in alpha/beta bands over brain regions implicated in cognitive processing, are consistent with increased cognitive network segregation in late onset LGS compared to typical age-onset LGS. Given network segregation is a normal aspect of brain maturation, these results imply that this process is less disturbed when the LGS process begins later in childhood.

A Multilayered GaAs IPD Resonator with Five Airbridges for Sensor System Application.

This work proposes a microwave resonator built from gallium arsenide using integrated passive device (IPD) technology. It consists of a three-layered interlaced spiral structure with airbridges and inner interdigital structures. For integrated systems, IPD technology demonstrated outstanding performance, robustness, and a tiny size at a low cost. The airbridges were made more compact, with overall dimensions of 1590 × 800 µm2 (0.038 × 0.019 λg2). The designed microwave resonator operated at 1.99 GHz with a return loss of 39 dB, an insertion loss of 0.07 dB, and a quality factor of 1.15. Additionally, an experiment was conducted on the properties of the airbridge and how they affected resistance, inductance, and S-parameters in the construction of the resonator. To investigate the impact of airbridges on the structure, E- and H-field distributions of the resonator were simulated. Furthermore, its use in sensing applications was explored. Various concentrations of glucose solutions were used in the experiment. The proposed device featured a minimum detectable concentration of 0.2 mg/mL; high sensitivity, namely, 14.58 MHz/mg·mL-1, with a linear response; and a short response time. Thus, this work proposes a structure that exhibits potential in integrated systems and real-time sensing systems with high sensitivity.

Clinical efficacy and metabolomic analysis of ozone major autohemotherapy for the treatment of herpes zoster.

Introduction: It is essential to understand the underlying changes in the patients' metabolic profiles that may be indicative of the therapy's effectiveness. Aim: To prospectively analyse the clinical efficacy of ozone autohemotherapy in the treatment of acute herpes zoster and investigate its impact on serum metabolomics. Material and methods: A total of 76 patients with acute herpes zoster between May 2018 and June 2020 were enrolled and divided into an experimental group and a control group. The pain location, Numeric Rating Scale (NRS) scores before and after treatment (1 week, 1 month, 3 months, and 6 months post-treatment), medication usage, and Quality of Sleep (QS) scores were prospectively analysed. Additionally, serum metabolomic data were obtained and analysed before and 6 months after the treatment. Results: There were statistically significant differences in the total NRS scores before and after ozone autohemotherapy (p < 0.05). The NRS scores of both groups significantly decreased (p < 0.05). At the 6-month follow-up, no patients were lost, and 83 patients completed the follow-up. The NRS improvement at 1 week, 1 month, 3 months, and 6 months post-treatment in the experimental group was significantly lower than that in the control group (p < 0.05). There was no significant difference in the medication usage (pregabalin or tramadol sustained-release tablets) between the two groups (p > 0.05). One month after treatment, the QS score improvement in the diabetes group was significantly lower than that in the non-diabetes group (p < 0.05). Serum metabolomics analysis revealed three significantly decreased metabolites, namely creatine, adipate, and glucose, after treatment. Conclusions: Ozone autohemotherapy is an effective treatment for acute herpes zoster patients and can rapidly and effectively alleviate pain symptoms in the short term. The changes in serum metabolomics may provide further insights into the treatment mechanism.

High-Definition Transcranial Direct Current Stimulation in the Right Ventrolateral Prefrontal Cortex Lengthens Sustained Attention in Virtual Reality.

Due to the current limitations of three-dimensional (3D) simulation graphics technology, mind wandering commonly occurs in virtual reality tasks, which has impeded it being applied more extensively. The right ventrolateral prefrontal cortex (rVLPFC) plays a vital role in executing continuous two-dimensional (2D) mental paradigms, and transcranial direct current stimulation (tDCS) over this cortical region has been shown to successfully modulate sustained 2D attention. Accordingly, we further explored the effects of electrical activation of the rVLPFC on 3D attentional tasks using anodal high-definition (HD)-tDCS. A 3D Go/No-go (GNG) task was developed to compare the after effects of real and sham brain stimulation. Specifically, GNG tasks were periodically interrupted to assess the subjective perception of attentional level, behavioral reactions were tracked and decomposed into an underlying decision cognition process, and electroencephalography data were recorded to calculate event-related potentials (ERPs) in rVLPFC. The p-values statistically indicated that HD-tDCS improved the subjective mentality, led to more cautious decisions, and enhanced neuronal discharging in rVLPFC. Additionally, the neurophysiological P300 ERP component and stimulation being active or sham could effectively predict several objective outcomes. These findings indicate that the comprehensive approach including brain stimulation, 3D mental paradigm, and cross-examined performance could significantly lengthen and robustly compare sustained 3D attention.

Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer.

Objective: Local invasion is the first step of metastasis, the main cause of colorectal cancer (CRC)-related death. Recent studies have revealed extensive intertumoral and intratumoral heterogeneity. Here, we focused on revealing local invasion-related genes in CRC. Methods: We used spatial transcriptomic techniques to study the process of local invasion in four CRC tissues. First, we compared the pre-cancerous, cancer center, and invasive margin in one section (S115) and used pseudo-time analysis to reveal the differentiation trajectories from cancer center to invasive margin. Next, we performed immunohistochemical staining for RPL5, STC1, AKR1B1, CD47, and HLA-A on CRC samples. Moreover, we knocked down AKR1B1 in CRC cell lines and performed CCK-8, wound healing, and transwell assays to assess cell proliferation, migration, and invasion. Results: We demonstrated that 13 genes were overexpressed in invasive clusters, among which the expression of CSTB and TM4SF1 was correlated with poor PFS in CRC patients. The ribosome pathway was increased, while the antigen processing and presentation pathway was decreased along CRC progression. RPL5 was upregulated, while HLA-A was downregulated along cancer invasion in CRC samples. Pseudo-time analysis revealed that STC1, AKR1B1, SIRPA, C4orf3, EDNRA, CES1, PRRX1, EMP1, PPIB, PLTP, SULF2, and EGFL6 were unpregulated along the trajectories. Immunohistochemic3al staining showed the expression of STC1, AKR1B1, and CD47 was increased along cancer invasion in CRC samples. Knockdown of AKR1B1 inhibited CRC cells' proliferation, migration, and invasion. Conclusions: We revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion.

Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma.

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.

Clinical study of Shenqi Dihuang Decoction and Xiaochengqi Decoction combined with hemodialysis in the treatment of the patients with CKD stage 5 and Qi and Yin deficiency and turbid poison inherent pattern / 国际中医中药杂志

Objective:To investigate the clinical effect of Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis in the treatment of qi deficiency, blood stasis and dampness and turbidity in chronic kidney disease (CKD) stage 5.Methods:Randomized controlled trial. A total of 102 elderly CKD stage 5 patients with Qi and Yin deficiency and turbid poison inherent type were selected from May 2021 to January 2022 of the Beijing Longfu Hospital. The patients were divided into two groups by random number table method. Control group (51 cases) received hemodialysis treatment for 4 weeks, and the observation group (51 cases) received Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis treatment for 4 weeks. The levels of BUN, SCr and β2-microglobulin (β2-MG), and K +, Ca 2+, P 3- content, hemoglobin were detected by automatic blood cell analyzer, and serum CRP and IL-6 levels were detected by latex enhanced immune scattering turbidimetry. The adverse reactions during the treatment and evaluate the clinical efficacy were observed and recorded. Results:During the treatment, 2 patients in the observation group withdrew from the study due to severe diarrhea, and other patients completed the study. There were significant differences in total response rate between observation group and control group [91.84%(45/49) vs. 74.51%(38/51); χ2=5.32, P=0.002]. After treatment, scores of lumbar and knee acerbity, tiredness and fatigue, edema, dizziness and tinnitus, fear of cold and warm, yellow face, dry stool and total score in observation group were significantly lower than those in the control group ( t=8.38, 13.44, 15.14, 13.09, 7.12, 7.73, 11.16, 11.45, P<0.01); the scores of SF-12-PCS and SF-12-MCS were significantly higher than those in the control group ( t=3.24, 4.22, P<0.01). After treatment, levels of serum BUN [(15.02±2.35)mmoL/L vs. (18.02±3.65)mmoL/L, t=4.87], SCr[(155.26±23.65) μmol/L vs. (184.49±35.49) μmol/L, t=4.83], β2-MG[(7.12±1.27)mg/L vs. (9.56±2.14)mg/L, t=6.90] and P 3-[(1.51±0.10) mmol/L vs. (2.02±0.19) mmol/L, t=16.70], K +[(3.65±0.54) mmol/L vs. (4.21±0.63)mmol/L, t=4.76] in observation group were significantly lower than those in the control group ( P<0.01); Ca 2+[(1.86±0.36)mmol/L vs. (2.35±0.42)mmol/L, t=6.25] was significantly higher than that of the control group ( P<0.01). No adverse reactions occurred during the treatment in the two groups ( P>0.05). Conclusion:Shenqi Dihuang Decoction and Xiaochengqi Decoction enema and hemodialysis can improve renal function, correct electrolyte disorder, reduce the level of inflammatory factors, improve the quality of life, and improve the therapeutic effect of the patients with CKD stage 5 and Qi and Yin deficiency and turbid poison inherent pattern.

Evaluating the Alterations Induced by Virtual Reality in Cerebral Small-World Networks Using Graph Theory Analysis with Electroencephalography.

Virtual reality (VR), a rapidly evolving technology that simulates three-dimensional virtual environments for users, has been proven to activate brain functions. However, the continuous alteration pattern of the functional small-world network in response to comprehensive three-dimensional stimulation rather than realistic two-dimensional media stimuli requires further exploration. Here, we aimed to validate the effect of VR on the pathways and network parameters of a small-world organization and interpret its mechanism of action. Fourteen healthy volunteers were selected to complete missions in an immersive VR game. The changes in the functional network in six different frequency categories were analyzed using graph theory with electroencephalography data measured during the pre-, VR, and post-VR stages. The mutual information matrix revealed that interactions between the frontal and posterior areas and those within the frontal and occipital lobes were strengthened. Subsequently, the betweenness centrality (BC) analysis indicated more robust and extensive pathways among hubs. Furthermore, a specific lateralized channel (O1 or O2) increment in the BC was observed. Moreover, the network parameters improved simultaneously in local segregation, global segregation, and global integration. The overall topological improvements of small-world organizations were in high-frequency bands and exhibited some degree of sustainability.

Brain network analysis of interictal epileptiform discharges from ECoG to identify epileptogenic zone in pediatric patients with epilepsy and focal cortical dysplasia type II: A retrospective study.

Objective: For patients with drug-resistant focal epilepsy, intracranial monitoring remains the gold standard for surgical intervention. Focal cortical dysplasia (FCD) is the most common cause of pharmacoresistant focal epilepsy in pediatric patients who usually develop seizures in early childhood. Timely removal of the epileptogenic zone (EZ) is necessary to achieve lasting seizure freedom and favorable developmental and cognitive outcomes to improve the quality of life. We applied brain network analysis to investigate potential biomarkers for the diagnosis of EZ that will aid in the resection for pediatric focal epilepsy patients with FCD type II. Methods: Ten pediatric patients with focal epilepsy diagnosed as FCD type II and that had a follow-up after resection surgery (Engel class I [n = 9] and Engel class II [n = 1]) were retrospectively included. Time-frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation were combined to calculate brain network parameters based on interictal epileptiform discharges from ECoG. Results: Clustering coefficient, local efficiency, node out-degree, and node out-strength with higher values are the most reliable biomarkers for the delineation of EZ, and the differences between EZ and margin zone (MZ), and EZ and normal zone (NZ) were significant (p < 0.05; Mann-Whitney U-test, two-tailed). In particular, the difference between MZ and NZ was significant for patients with frontal FCD (MZ > NZ; p < 0.05) but was not significant for patients with extra-frontal FCD. Conclusions: Brain network analysis, based on the combination of time-frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation, can aid in the diagnosis of EZ for pediatric focal epilepsy patients with FCD type II.

Alteration in brain connectivity in patients with Dravet syndrome after vagus nerve stimulation (VNS): exploration of its effectiveness using graph theory analysis with electroencephalography.

OBJECTIVE: Vagus nerve stimulation (VNS) is a nonpharmacologic therapeutic option for patients who have pharmaco-resistant Dravet syndrome (DS). Plentiful efforts have been made for delivering VNS to DS patients, but its effectiveness still requires further verification. We investigated the effectiveness of the VNS treatment of DS patients using brain connectivity analysis with electroencephalography (EEG). APPROACH: Twenty pharmaco-resistant DS patients were selected to undergo VNS implantation and classified into responder and non-responder groups after 24 months post-VNS. The effect of VNS between 6 months pre- and 6, 12, and 24 months post-VNS in all patients, responders, and non-responders on four different frequency categories of four brain parameters were compared using resting-state EEG. MAIN RESULTS: In alpha and beta bands, all patients showed positive results for characteristic path length (CPL), global efficiency (GE), and transitivity after VNS treatment, and changes in betweenness centrality (BC) were not significant. The difference in transitivity between responders and non-responders is more pronounced than those in CPL and GE are, in both the alpha (p < 0.015) and beta (p < 0.001) bands. There was an obvious change in BC, especially in the alpha band, as the hubs tended to move from frontal lobe to parietal lobe for responders; however, there was no change for the non-responders. SIGNIFICANCE: We investigated the alteration in brain connectivity of DS patients in alpha and beta bands during a long-term follow-up and found the responders have a decreased transitivity after the VNS treatment. Moreover, the hubs with high values in the alpha band tended to move from frontal lobe to parietal lobe for responders after VNS treatment.

Identification of epigenetic factor KAT2B gene variants for possible roles in congenital heart diseases.

Congenital heart disease (CHD) is a group of anatomic malformations in the heart with high morbidity and mortality. The mammalian heart is a complex organ, the formation and development of which are strictly regulated and controlled by gene regulatory networks of many signaling pathways such as TGF-ß. KAT2B is an important histone acetyltransferase epigenetic factor in the TGF-ß signaling pathway, and alteration in the gene is associated with the etiology of cardiovascular diseases. The aim of this work was to validate whether KAT2B variations might be associated with CHD. We sequenced the KAT2B gene for 400 Chinese Han CHD patients and evaluated SNPs rs3021408 and rs17006625. The statistical analyses and Hardy-Weinberg equilibrium tests of the CHD and control populations were conducted by the software SPSS (version 19.0) and PLINK. The experiment-wide significance threshold matrix of LD correlation for the markers and haplotype diagram of LD structure were calculated using the online software SNPSpD and Haploview software. We analyzed the heterozygous variants within the CDS region of the KAT2B genes and found that rs3021408 and rs17006625 were associated with the risk of CHD.

Fabrication of QFN-Packaged Miniaturized GaAs-Based Bandpass Filter with Intertwined Inductors and Dendritic Capacitor.

This article presents a compact quad flat no-lead (QFN)-packaged second-order bandpass filter (BPF) with intertwined inductors, a dendritic capacitor, and four air-bridge structures, which was fabricated on a gallium arsenide (GaAs) substrate by integrated passive device (IPD) technology. Air-bridge structures were introduced into an approximate octagonal outer metal track to provide a miniaturized chip size of 0.021 × 0.021 λ0 (0.8 × 0.8 mm2) for the BPF. The QFN-packaged GaAs-based bandpass filter was used to protect the device from moisture and achieve good thermal and electrical performances. An equivalent circuit was modeled to analyze the BPF. A description of the manufacturing process is presented to elucidate the physical structure of the IPD-based BPF. Measurements were performed on the proposed single band BPF using a center frequency of 2.21 GHz (return loss of 26.45 dB) and a 3-dB fractional bandwidth (FBW) of 71.94% (insertion loss of 0.38 dB). The transmission zero is located at the 6.38 GHz with a restraint of 30.55 dB. The manufactured IPD-based BPF can play an excellent role in various S-band applications, such as a repeater, satellite communication, and radar, owing to its miniaturized chip size and high performance.

Tailored Biofunctionalized Biosensor for the Label-Free Sensing of Prostate-Specific Antigen.

The increase in the demand and popularity of smart biosensors has brought a novel and innovative concept to develop a diverse range of semen mutual biomarker (i.e., prostate-specific antigen, PSA)-based biodevices for our daily life applications. Using a versatile strategy, here we have developed a next-generation miniaturized capacitive biomarker-based sensor, which facilitates a direct, rapid quantitation and ultrafast detection of prostate-specific antigen (PSA) selectively. To fabricate an affordable PSA biosensor, an interdigitated capacitor (IDC) was functionalized and to detect PSA at concentrations varying from 0.1 to 10 µL/mL, with a response time of 3 s. Moreover, the PSA biosensor showed a high level of selectivity due to the successful probing of the capacitive response-generated biomolecular interactions using external stimuli at the bioelectrode. The resulting IDC-based PSA biosensors are capable of excellent reproducibility and reusability, which are required for real-time biosensing of any targeted biomolecules where low-concentration detection is a key for point-of-care, on-site sensing applications. We anticipate that this research could open exciting opportunities for PSA detection at a low concentration level.

Diagnosis and treatment of ankyloglossia in newborns and infants / 华西口腔医学杂志

Ankyloglossia is a congenital condition characterized by a short lingual frenulum, which may result in the restriction of tongue movement and function. Considerable controversy regarding the diagnosis, clinical significance, and management of the condition remains, and great variations in practice have been recorded. Indeed, attitudes toward ankyloglossia differ among professional groups, and opinions may vary remarkably even among those within the same specialty. This article reviews the embryology, genetics, diagnosis, clinical presentation, and treatment of ankyloglossia to help physicians better understand and treat the condition.

On-Chip Miniaturized Bandpass Filter Using GaAs-Based Integrated Passive Device Technology For L-Band Application.

In this work, a miniaturized bandpass filter (BPF) constructed of two spiral intertwined inductors and a central capacitor, with several interdigital structures, was designed and fabricated using integrated passive device (IPD) technology on a GaAs wafer. Five air-bridge structures were introduced to enhance the mutual inductive effect and form the differential geometry of the outer inductors. In addition, the design of the differential inductor combined with the centrally embedded capacitor results in a compact construction with the overall size of 0.037λ0 × 0.019λ0 (1537.7 × 800 µm2) where λ0 is the wavelength of the central frequency. For the accuracy evolution of the equivalent circuit, the frequency-dependent lumped elements of the proposed BPF was analyzed and modeled through the segment method, mutual inductance approach, and simulated scattering parameters (S-parameters). Afterward, the BPF was fabricated using GaAs-based IPD technology and a 16-step manufacture flow was accounted for in detail. Finally, the fabricated BPF was wire-bonded with Au wires and packaged onto a printed circuit board for radio-frequency performance measurements. The measured results indicate that the implemented BPF possesses a center frequency operating at 2 GHz with the insertion losses of 0.38 dB and the return losses of 40 dB, respectively, and an ultrawide passband was achieved with a 3-dB fraction bandwidth of 72.53%, as well. In addition, a transmission zero is located at 5.32 GHz. Moreover, the variation of the resonant frequency with different inductor turns and metal thicknesses was analyzed through the simulation results, demonstrating good controllability of the proposed BPF.

Exploration into the simplex reinforcing-reducing manipulation of acupuncture / 中国针灸

Four controversial types of simplex reinforcing-reducing manipulation of acupuncture and their possible meanings were summarized to explore several key elements of reinforcing-reducing manipulation of acupuncture, in addition, the simplex reinforcing-reducing manipulation of acupuncture was classified by single factor. It is concluded that the definition of simplex reinforcing-reducing manipulation of acupuncture should try not to include other non-manipulative elements. According to single factor, it can be divided into: needle-oriented reinforcing-reducing manipulation, twisting reinforcing-reducing manipulation, lifting and interpolating reinforcing-reducing manipulation, fast and slow reinforcing-reducing manipulation, breathing reinforcing-reducing manipulation, opening and closing reinforcing-reducing manipulation. In addition, after considering the effect and principle of number reinforcing-reducing manipulation, it can be considered.

Progress of the application of PET technology in acupuncture research / 中国针灸

To further investigate the application of positron emission tomography (PET) technology in acupuncture research field, with "PET" and "acupuncture" as keywords, the related literature published from 1997 to 2018 was searched in PubMed, CNKI and WANFANG database; then the literature was classified and analyzed. The results showed that in clinical and experimental studies, whether in physiological or pathological conditions, PET technology has verified the specificity of acupoints, bidirectional regulation of acupoints, and the clinical effect of -arrival from the level of brain functional activity. It has deeply revealed the central mechanism underlying that acupuncture has multi-target, multi-channel and multi-level overall effects. The purpose of this study is to provide objective scientific basis for acupuncture research, and then potentially guide the clinical practice.

A High-Frequency-Compatible Miniaturized Bandpass Filter with Air-Bridge Structures Using GaAs-Based Integrated Passive Device Technology.

This paper reports on the use of gallium arsenide-based integrated passive device technology for the implementation of a miniaturized bandpass filter that incorporates an intertwined circle-shaped spiral inductor and an integrated center-located capacitor. Air-bridge structures were introduced to the outer inductor and inner capacitor for the purpose of space-saving, thereby yielding a filter with an overall chip area of 1178 µm × 970 µm. Thus, not only is the chip area minimized, but the magnitude of return loss is also improved as a result of selective variation of bridge capacitance. The proposed device possesses a single passband with a central frequency of 1.71 GHz (return loss: 32.1 dB), and a wide fractional bandwidth (FBW) of 66.63% (insertion loss: 0.50 dB). One transmission zero with an amplitude of 43.42 dB was obtained on the right side of the passband at 4.48 GHz. Owing to its miniaturized chip size, wide FBW, good out-band suppression, and ability to yield high-quality signals, the fabricated bandpass filter can be implemented in various L-band applications such as mobile services, satellite navigation, telecommunications, and aircraft surveillance.

Effects of Educational Counseling as Solitary Therapy for Chronic Primary Tinnitus and Related Problems.

The aim of this study was to evaluate the early and sustained effects of tinnitus educational counseling on chronic primary tinnitus and related problems. A descriptive longitudinal cohort study was conducted with 159 adult patients suffering from chronic primary tinnitus and sleep problems. All patients received tinnitus educational counseling, sleep adjustment, and vegan dietary advice. At short-term assessment within 3 months and long-term follow-up at 6-26 months, perceived changes in tinnitus were assessed with the Tinnitus Handicap Inventory (THI) and the Tinnitus Evaluation Questionnaire (TEQ), respectively. In TEQ, the volume of subjective tinnitus was scored according to realistic environments in which tinnitus could be heard. Sleep quality was assessed with questionnaires developed in our laboratory. Most of the subjects showed significant early improvement in their THI scores (96/159, 60.38%; from 46.11 ± 22.74 to 31.94 ± 20.41, t = 11.16, p < 0.001, Cohen's d = 0.66). Tinnitus volume (39/159, 24.53%, from 2,2 to 2,1, z = -3.56, p < 0.001) and sleep quality (68/159, 42.77%; from 7.13 ± 3.11 to 6.31 ± 2.75, t = 3.73, p < 0.001, Cohen's d = 0.28) were also improved. Long-term follow-up TEQ results indicated that tinnitus loudness, the impact of tinnitus on sleep, concentration, and emotional state were all improved since the prior consultation (p = 0.001, 0.026, 0.012, and <0.001). Short-term improvement of tinnitus severity correlated directly with improvement of sleep quality (odds ratio (OR) = 0.30, 95% confidence interval (CI): 0.14-0.64, p = 0.002), initial THI score (OR = 1.02, 95% CI: 1.01 to 1.04, p = 0.006), compliance with sleep advice (OR = 2.27, 95% CI: 1.02-5.05, p = 0.044), and nervous disposition (OR = 2.80, 95% CI: 1.25-6.30, p = 0.013). A future randomized controlled trial would be carried out to examine the effect of sole tinnitus educational counseling.

Highly Selective Pd-Catalyzed Direct C-F Bond Arylation of Polyfluoroarenes.

A directing-group-free palladium-catalyzed direct arylation of simple polyfluoroarenes with arylboronic acids through selective C-F bond activation is described. The combination of Pd(OAc)2 with BrettPhos was identified as an efficient catalytic system to promote the reaction with high regioselectivity and broad substrate scope. Preliminary mechanistic studies reveal that the oxidative addition of Pd to the C-F bond is involved in the catalytic cycle.