Successful interventional occlusion of muscular ventricular septal defect in a dog.

Ventricular septal defect (VSD) is a rare congenital heart disease in dogs. Hemodynamically important interventricular defects must be closed to improve the prognosis. This case report describes successful interventional transcatheter closure of a muscular VSD in a young Maltese and poodle mixed-breed dog with a large muscular interventricular defect (~5 mm in diameter) with a high rate of left-to-right shunt flow. The VSD was closed with a customized Amplatzer-type VSD occluder via a percutaneous transvenous (jugular) approach. We concluded that interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs. A regular follow-up study for this dog is ongoing and has not detected complications. Key clinical message: Interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs.

Occlusion interventionnelle réussie d'une communication interventriculaire musculaire chez un chien. La communication interventriculaire (VSD) est une maladie cardiaque congénitale rare chez le chien. Les anomalies interventriculaires hémodynamiquement importantes doivent être fermées pour améliorer le pronostic. Ce rapport de cas décrit la fermeture interventionnelle réussie par cathéter d'un VSD musculaire chez un jeune chien de race mixte (maltais et caniche) présentant un défaut interventriculaire musculaire important (~5 mm de diamètre) avec un débit de shunt élevé de gauche à droite. Le VSD a été fermé avec un obturateur VSD personnalisé de type Amplatzer via une approche trans-veineuse percutanée (jugulaire). Nous avons conclu que l'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens. Une étude de suivi régulière de ce chien est en cours et aucune complication n'a été détectée.Message clinique clé :L'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens.(Traduit par Dr Serge Messier).

Ecdysone-induced microRNA miR-276a-3p controls developmental growth by targeting the insulin-like receptor in Drosophila.

Animal growth is controlled by a variety of external and internal factors during development. The steroid hormone ecdysone plays a critical role in insect development by regulating the expression of various genes. In this study, we found that fat body-specific expression of miR-276a, an ecdysone-responsive microRNA (miRNA), led to a decrease in the total mass of the larval fat body, resulting in significant growth reduction in Drosophila. Changes in miR-276a expression also affected the proliferation of Drosophila S2 cells. Furthermore, we found that the insulin-like receptor (InR) is a biologically relevant target gene regulated by miR-276a-3p. In addition, we found that miR-276a-3p is upregulated by the canonical ecdysone signalling pathway involving the ecdysone receptor and broad complex. A reduction in cell proliferation caused by ecdysone was compromised by blocking miR-276a-3p activity. Thus, our results suggest that miR-276a-3p is involved in ecdysone-mediated growth reduction by controlling InR expression in the insulin signalling pathway.

Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant.

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

Thermotropic Liquid-Crystalline and Light-Emitting Properties of Bis(4-aalkoxyphenyl) Viologen Bis(triflimide) Salts.

A series of bis(4-alkoxyphenyl) viologen bis(triflimide) salts with alkoxy chains of different lengths were synthesized by the metathesis reaction of respective bis(4-alkoxyphenyl) viologen dichloride salts, which were in turn prepared from the reaction of Zincke salt with the corresponding 4-n-alkoxyanilines, with lithium triflimide in methanol. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance spectra and elemental analysis. Their thermotropic liquid-crystalline (LC) properties were examined by differential scanning calorimetry, polarizing optical microscopy, and variable temperature X-ray diffraction. Salts with short length alkoxy chains had crystal-to-liquid transitions. Salts of intermediate length alkoxy chains showed both crystal-to-smectic A (SmA) transitions, Tms, and SmA-to-isotropic transitions, Tis. Those with longer length of alkoxy chains had relatively low Tms at which they formed the SmA phases that persisted up to the decomposition at high temperatures. As expected, all of them had excellent thermal stabilities in the temperature range of 330-370 °C. Their light-emitting properties in methanol were also included.

Identification of Alzheimer's disease and mild cognitive impairment using multimodal sparse hierarchical extreme learning machine.

Different modalities such as structural MRI, FDG-PET, and CSF have complementary information, which is likely to be very useful for diagnosis of AD and MCI. Therefore, it is possible to develop a more effective and accurate AD/MCI automatic diagnosis method by integrating complementary information of different modalities. In this paper, we propose multi-modal sparse hierarchical extreme leaning machine (MSH-ELM). We used volume and mean intensity extracted from 93 regions of interest (ROIs) as features of MRI and FDG-PET, respectively, and used p-tau, t-tau, and Aß42 as CSF features. In detail, high-level representation was individually extracted from each of MRI, FDG-PET, and CSF using a stacked sparse extreme learning machine auto-encoder (sELM-AE). Then, another stacked sELM-AE was devised to acquire a joint hierarchical feature representation by fusing the high-level representations obtained from each modality. Finally, we classified joint hierarchical feature representation using a kernel-based extreme learning machine (KELM). The results of MSH-ELM were compared with those of conventional ELM, single kernel support vector machine (SK-SVM), multiple kernel support vector machine (MK-SVM) and stacked auto-encoder (SAE). Performance was evaluated through 10-fold cross-validation. In the classification of AD vs. HC and MCI vs. HC problem, the proposed MSH-ELM method showed mean balanced accuracies of 96.10% and 86.46%, respectively, which is much better than those of competing methods. In summary, the proposed algorithm exhibits consistently better performance than SK-SVM, ELM, MK-SVM and SAE in the two binary classification problems (AD vs. HC and MCI vs. HC).

Kudzu Leaf Extract Suppresses the Production of Inducible Nitric Oxide Synthase, Cyclooxygenase-2, Tumor Necrosis Factor-Alpha, and Interleukin-6 via Inhibition of JNK, TBK1 and STAT1 in Inflammatory Macrophages.

Kudzu (Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep) is a perennial leguminous vine, and its root and flower have been used for herbal medicine in Asia for a long time. Most dietary flavonoids are reported to be concentrated in its root, not in its aerial parts including leaves. In this study, we investigated whether kudzu leaf and its major constituent, robinin (kaempferol-3-O-robinoside-7-O-rhanmoside) possessed anti-inflammatory activity. To test this hypothesis, we used peritoneal macrophages isolated from BALB/c mice and stimulated the cells with lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ. Compared with kudzu root extract, its leaf extract was more potent in inhibiting the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6. Kudzu leaf extract decreased LPS-induced activation of c-Jun N-terminal kinase (JNK) and TANK-binding kinase 1(TBK1) with no effects on nuclear factor-κB and activator protein 1 transcriptional activity. Also, kudzu leaf extract inhibited LPS/IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) activation partly via an altered level of STAT1 expression. Robinin, being present in 0.46% of dry weight of leaf extract, but almost undetected in the root, decreased iNOS protein involving modulation of JNK and STAT1 activation. However, robinin showed no impact on other inflammatory markers. Our data provide evidence that kudzu leaf is an excellent food source of as yet unknown anti-inflammatory constituents.

Re-configurable, multi-mode contained-electrospray ionization for protein folding and unfolding on the millisecond time scale.

A new reconfigurable contained-electrospray (ES) ion source is described that can be operated in three unique modes (Types I, II and III) and was applied to control the charge state of proteins for subsequent online characterization by mass spectrometry. Using this device, proteins prepared in 100% water were highly charged after exposure to hydrochloric acid vapor. For myoglobin, the shift to a higher charge state occurred faster than the heme cofactor could escape the unfolding protein. This effect reflected in the detection of highly charged holo-myoglobin intermediates (+26), which suggests the modification process occurred on a millisecond time scale (Type I mode). By introducing a cavity in the contained-ES emitter (Type II mode), increased protein denaturation was observed where only apo-myoglobin ions were detected. A similar increase in the charge effect was observed for less pH sensitive proteins such as ubiquitin and cytochrome c. In a third type of experiment, acidified aqueous-based droplets containing unfolded proteins were briefly exposed to aqueous ammonium acetate/triethylammonium acetate solution mixtures to increase the droplet pH and to induce protein folding during electrospray ionization. Charge-state distributions showed protein folding occurred, including the appearance of charged reduced species that were not observed when sprayed in pure water. The three operational modes of contained-electrospray allow online modification of an analyte during charge droplet formation using both vapor and non-volatile liquid reagents, without a direct addition of the modifying reagent to the analyte solution.

A real-time pinch-to-zoom motion detection by means of a surface EMG-based human-computer interface.

In this paper, we propose a system for inferring the pinch-to-zoom gesture using surface EMG (Electromyography) signals in real time. Pinch-to-zoom, which is a common gesture in smart devices such as an iPhone or an Android phone, is used to control the size of images or web pages according to the distance between the thumb and index finger. To infer the finger motion, we recorded EMG signals obtained from the first dorsal interosseous muscle, which is highly related to the pinch-to-zoom gesture, and used a support vector machine for classification between four finger motion distances. The powers which are estimated by Welch's method were used as feature vectors. In order to solve the multiclass classification problem, we applied a one-versus-one strategy, since a support vector machine is basically a binary classifier. As a result, our system yields 93.38% classification accuracy averaged over six subjects. The classification accuracy was estimated using 10-fold cross validation. Through our system, we expect to not only develop practical prosthetic devices but to also construct a novel user experience (UX) for smart devices.

Analysis of factors associated with patients' global impression of change scores in inpatients with peripheral facial palsy: A retrospective study at a Korean Medicine Hospital.

The incidence of peripheral facial palsy is on the rise, with psychological issues influencing quality of life due to visible symptoms. Consequently, patient-reported outcome measures are critical in assessing the disease burden and the treatment efficacy of peripheral facial palsy from patients' perspective. This study examines factors influencing patients' global impression of change (PGIC) scores, a type of patient-reported outcome measure, in hospitalized patients with peripheral facial palsy. This retrospective study analyzed the electronic medical records of 200 patients with peripheral facial palsy who were admitted to the Korean Medicine Hospital, Kyung Hee University Medical Center from May 1, 2022 to April 30, 2023. Impact of demographic, electrophysiological, intervention, and clinical factors on PGIC scores were evaluated. Descriptive statistics showed that the length of hospitalization (P = .020), time from disease onset to hospitalization (P = .022), lacrimal disorders (P = .002), House-Brackmann (HB) grade evaluated at admission (P = .016) and at discharge (P < .001), improvement in HB-grade from admission to discharge (P = .002), and total facial disability index (FDI) score at discharge (P < .001) were significantly associated with PGIC scores. In multivariate logistic regression analysis, HB-grade at admission (OR: 13.89, 95% CI: 2.18-113.60), length of stay (OR: 0.27, 95% CI: 0.07-0.92), time from disease onset to hospitalization (OR: 5.55, 95% CI: 1.36-24. 77), tear-related symptoms (OR: 0.41, 95% CI: 0.17-0.96), total FDI score (OR: 0.45, 95% CI: 0.20-0.98), and greater improvement in HB-grade at discharge compared to admission (OR: 0.08, 95% CI: 0.02-0.31) were significantly associated with PGIC scores. Patients with milder initial disease severity, hospitalization period exceeding 7 days, shorter time from disease onset to hospitalization, improvement of lacrimal symptoms, total FDI score, and HB-grade between admission and discharge experienced more significant subjective improvement in peripheral facial palsy.

Blood Pressure Measurement Based on the Camera and Inertial Measurement Unit of a Smartphone: Instrument Validation Study.

Background: Even though several mobile apps that can measure blood pressure have been developed, the data about the accuracy of these apps are limited. Objective: We assessed the accuracy of AlwaysBP (test) in blood pressure measurement compared with the standard, cuff-based, manual method of brachial blood pressure measurement (reference). Methods: AlwaysBP is a smartphone software that estimates systolic blood pressure (SBP) and diastolic blood pressure (DBP) based on pulse transit time (PTT). PTT was calculated with a finger photoplethysmogram and seismocardiogram using, respectively, the camera and inertial measurement unit sensor of a commercially available smartphone. After calculating PTT, SBP and DBP were estimated via the Bramwell-Hill and Moens-Korteweg equations. A calibration process was carried out 3 times for each participant to determine the input parameters of the equations. This study was conducted from March to August 2021 at Chungnam National University Sejong Hospital with 87 participants aged between 19 and 70 years who met specific conditions. The primary analysis aimed to evaluate the accuracy of the test method compared with the reference method for the entire study population. The secondary analysis was performed to confirm the stability of the test method for up to 4 weeks in 15 participants. At enrollment, gender, arm circumference, and blood pressure distribution were considered according to current guidelines. Results: Among the 87 study participants, 45 (52%) individuals were male, and the average age was 35.6 (SD 10.4) years. Hypertension was diagnosed in 14 (16%) participants before this study. The mean test and reference SBPs were 120.0 (SD 18.8) and 118.7 (SD 20.2) mm Hg, respectively (difference: mean 1.2, SD 7.1 mm Hg). The absolute differences between the test and reference SBPs were <5, <10, and <15 mm Hg in 57.5% (150/261), 84.3% (220/261 ), and 94.6% (247/261) of measurements. The mean test and reference DBPs were 80.1 (SD 12.6) and 81.1 (SD 14.4) mm Hg, respectively (difference: mean -1.0, SD 6.0 mm Hg). The absolute differences between the test and reference DBPs were <5, <10, and <15 mm Hg in 75.5% (197/261), 93.9% (245/261), and 97.3% (254/261) of measurements, respectively. The secondary analysis showed that after 4 weeks, the differences between SBP and DBP were 0.1 (SD 8.8) and -2.4 (SD 7.6) mm Hg, respectively. Conclusions: AlwaysBP exhibited acceptable accuracy in SBP and DBP measurement compared with the standard measurement method, according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization protocol criteria. However, further validation studies with a specific validation protocol designed for cuffless blood pressure measuring devices are required to assess clinical accuracy. This technology can be easily applied in everyday life and may improve the general population's awareness of hypertension, thus helping to control it.

Acupuncture for the treatment of trigeminal neuralgia: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Few systematic reviews have examined the effects of acupuncture on trigeminal neuralgia. This review aims to provide up-to-date evidence on the efficacy of acupuncture for managing pain in patients with trigeminal neuralgia. METHODS: Eleven databases were searched from inception until November 2022 for relevant articles Two researchers independently conducted study selection, data extraction, and evaluation. The present review solely targeted randomized controlled trials (RCTs). The Cochrane risk of bias assessment tool 2.0 was employed to assess the risk of bias. Data were compiled using RevMan 5.4.1 software, and the quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Thirty studies involving 2295 patients were included in this review. Compared with carbamazepine, acupuncture led to improvements in pain scores (15 RCTs, mean difference (MD) - 1.40, 95% confidence interval (CI)-1.82 to -0.98 [95% prediction interval, -3.137,0.343], p < 0.00001, low certainty of evidence (CoE)), response rates (29 RCTs, risk ratio (RR) 1.20, 95% CI 1.15 to 1.25 [95% prediction interval, 1.067, 1.346], p < 0.00001, low CoE), frequency of pain attacks (2 RCTs, MD -2.53, 95% CI -4.11 to -0.96, P = 0.002, low CoE), and adverse effects (13 RCTs, risk difference (RD) -0.15, 95% CI -0.19 to -0.11 [95% prediction interval, -0.193, -0.108], P < 0.00001, very low CoE). CONCLUSION: Although the quality of evidence is low, compared with carbamazepine, acupuncture may improve trigeminal neuralgia-related pain. Further rigorously designed studies are warranted to confirm the effects of acupuncture on patients with trigeminal neuralgia.

Acupuncture for the treatment of tinnitus: a systematic review of randomized clinical trials.

BACKGROUND: Complementary and alternative medicine (CAM) has frequently been used to treat tinnitus, and acupuncture is a particularly popular option. The objective of this review was to assess the evidence concerning the effectiveness of acupuncture as a treatment for tinnitus. METHODS: Fourteen databases were searched from the dates of their creation to July 4th, 2012. Randomized clinical trials (RCTs) were included if acupuncture was used as the sole treatment. The Cochrane risk of bias tool was used to assess the risk of bias. RESULTS: A total of 9 RCTs met all the inclusion criteria. Their methodological quality was mostly poor. Five RCTs compared the effectiveness of acupuncture or electroacupuncture with sham acupuncture for treating tinnitus. The results failed to show statistically significant improvements. Two RCTs compared a short one-time scalp acupuncture treatment with the use of penetrating sham acupuncture at non-acupoints in achieving subjective symptom relief on a visual analog scale; these RCTs demonstrated significant positive effects with scalp acupuncture. Two RCTs compared acupuncture with conventional drug treatments. One of these RCTs demonstrated that acupuncture had statistically significant effects on the response rate in patients with nervous tinnitus, but the other RCT did not demonstrate significant effects in patients with senile tinnitus. CONCLUSIONS: The number, size and quality of the RCTs on the effectiveness of acupuncture for the treatment of tinnitus are not sufficient for drawing definitive conclusions. Further rigorous RCTs that overcome the many limitations of the current evidence are warranted.

Vowel speech recognition from rat electroencephalography using long short-term memory neural network.

Over the years, considerable research has been conducted to investigate the mechanisms of speech perception and recognition. Electroencephalography (EEG) is a powerful tool for identifying brain activity; therefore, it has been widely used to determine the neural basis of speech recognition. In particular, for the classification of speech recognition, deep learning-based approaches are in the spotlight because they can automatically learn and extract representative features through end-to-end learning. This study aimed to identify particular components that are potentially related to phoneme representation in the rat brain and to discriminate brain activity for each vowel stimulus on a single-trial basis using a bidirectional long short-term memory (BiLSTM) network and classical machine learning methods. Nineteen male Sprague-Dawley rats subjected to microelectrode implantation surgery to record EEG signals from the bilateral anterior auditory fields were used. Five different vowel speech stimuli were chosen, /a/, /e/, /i/, /o/, and /u/, which have highly different formant frequencies. EEG recorded under randomly given vowel stimuli was minimally preprocessed and normalized by a z-score transformation to be used as input for the classification of speech recognition. The BiLSTM network showed the best performance among the classifiers by achieving an overall accuracy, f1-score, and Cohen's κ values of 75.18%, 0.75, and 0.68, respectively, using a 10-fold cross-validation approach. These results indicate that LSTM layers can effectively model sequential data, such as EEG; hence, informative features can be derived through BiLSTM trained with end-to-end learning without any additional hand-crafted feature extraction methods.

Electroacupuncture for the treatment of frozen shoulder: A systematic review and meta-analysis.

Background: Electroacupuncture (EA) has reportedly been successful in controlling pain, but there have been no systematic reviews examining the impact of EA on patients with frozen shoulder (FS). The purpose of this review is to provide evidence on the safety and efficacy of EA for pain management in patients with FS. Methods: We searched 11 databases from their inception: EMBASE, the Cochrane Library, PubMed, AMED, one Chinese medical database, and six Korean medical databases. Two researchers independently performed the study selection, data extraction, and assessment. Bias-related risk was evaluated using the Cochrane risk-of-bias assessment tool. Results: This review included thirteen studies involving 936 patients. The EA group exhibited improvements in FS pain (MD -1.11, 95% CI -1.61 to -0.61, p < 0.0001, I 2 = 97%), function (SMD 2.02, 95% CI 0.36-3.69, p < 0.00001, I 2 = 97%), and response rates (RR 1.16, 95% CI 1.07-1.25; p = 0.0002; I 2 = 0%) over the manual acupuncture (MA) group. As an adjunct treatment, EA improved FS pain (SMD -1.12, 95% CI -1.52 to -0.71, P < 0.00001, I 2 = 0) compared to the control treatments. No adverse effects were reported. Conclusion: EA is reported to improve FS pain and function compared with control treatments. Additionally, EA can be used as an adjunct therapy for FS pain. EA could emerge as a potent intervention against FS. Systematic review registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021247090], identifier [CRD42021247090].

Acupuncture for the treatment of overactive bladder: A systematic review and meta-analysis.

Background: Acupuncture (AT) successfully regulates overactive bladder (OAB) symptoms. However, previous systematic reviews and meta-analyses have not provided sufficient evidence. This review presents the current evidence of the efficacy of AT in the management of OAB symptoms. Methods and analyses: A total of 12 databases were searched from their inception: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and AMED databases; five Korean medical databases; and three Chinese medical databases. Study selection, data extraction, and assessment were independently performed by two researchers. The risk of bias was assessed using the Cochrane risk of bias assessment tool. RevMan 5.4.1 software was used for data aggregation, and the Grades of Recommendations, Assessment, Development and Evaluation (GRADE) assessment was used to evaluate the quality of the study outcomes. Results: A total of 30 studies were included in this review. Compared with the sham AT group, the AT group exhibited significant effects in reducing overactive bladder symptom scores (OABSS) [mean difference (MD): -1.13, 95% confidence interval (CI): -2.01 to -0.26, p = 0.01 I 2 = 67%] and urinary frequency [standardized mean difference (SMD): -0.35, 95% CI: -0.62 to -0.08, I 2 = 0%]. The AT group showed an equivalent effect as drug therapy in reducing OABSS (MD: -0.39, 95% CI: - 1.92 to 1.13, p = 0.61, I 2 = 94%) and urinary frequency (MD: 0.74, 95% CI: -0.00 to 1.48, p = 0.05, I 2 = 71%) with fewer adverse events [risk ratio (RR): 0.38, 95% CI: 0.16-0.92, p = 0.03, I2 = 58%]. The AT plus drug therapy group had a more favorable effect than drug therapy alone for reducing OABSS (MD: -2.28, 95% CI: -3.25 to -1.31, p < 0.00001, I 2 = 84%) and urinary frequency (MD: -2.34, 95% CI: -3.29 to -1.38, p < 0.00001, I 2 = 88%). The GRADE assessment demonstrated that the level of evidence was mostly low or very low given the high risk of bias and small sample sizes. Conclusion: AT had more favorable effects than sham AT in reducing OAB symptoms. AT improved OAB symptoms as effectively as conventional drug therapy, and the combination of AT and drug therapy had more favorable effects than drug therapy alone. However, more rigorous studies are needed to enhance the level of evidence. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42014010377, identifier: PROSPERO [CRD42014010377].

Temsirolimus Enhances Anti-Cancer Immunity by Inducing Autophagy-Mediated Degradation of the Secretion of Small Extracellular Vesicle PD-L1.

Tumor-derived small extracellular vesicle (sEV) programmed death-ligand 1 (PD-L1) contributes to the low reactivity of cells to immune checkpoint blockade therapy (ICBT), because sEV PD-L1 binds to programmed death 1 (PD-1) in immune cells. However, there are no commercially available anti-cancer drugs that activate immune cells by inhibiting tumor-derived sEV PD-L1 secretion and cellular PD-L1. Here, we aimed to investigate if temsirolimus (TEM) inhibits both sEV PD-L1 and cellular PD-L1 levels in MDA-MB-231 cells. In cancer cell autophagy activated by TEM, multivesicular bodies (MVBs) associated with the secretion of sEV are degraded through colocalization with autophagosomes or lysosomes. TEM promotes CD8+ T cell-mediated anti-cancer immunity in co-cultures of CD8+ T cells and tumor cells. Furthermore, the combination therapy of TEM and anti-PD-L1 antibodies enhanced anti-cancer immunity by increasing both the number and activity of CD4+ and CD8+ T cells in the tumor and draining lymph nodes (DLNs) of breast cancer-bearing immunocompetent mice. In contrast, the anti-cancer effect of the combination therapy with TEM and anti-PD-L1 antibodies was reversed by the injection of exogenous sEV PD-L1. These findings suggest that TEM, previously known as a targeted anti-cancer drug, can overcome the low reactivity of ICBT by inhibiting sEV PD-L1 and cellular PD-L1 levels.

Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Acupuncture treatment of a patient with persistent allergic rhinitis complicated by rhinosinusitis and asthma.

A pathophysiologic relationship between allergic rhinitis and rhinosinusitis and asthma has long been suggested. However, few clinical studies of acupuncture have been conducted on these comorbid conditions. A 48-year-old male suffering from persistent allergic rhinitis with comorbid chronic rhinosinusitis and asthma since the age of 18 years was studied. He complained of nasal obstruction, sneezing, cough, rhinorrhea and moderate dyspnea. He occasionally visited local ear-nose-throat clinics for his nasal symptoms, but gained only periodic symptom relief. The patient was treated with acupuncture, infrared radiation to the face and electro-acupuncture. Needles were inserted at bilateral LI20, GV23, LI4 and EX-1 sites with De-qi. Electro-acupuncture was performed simultaneously at both LI20 sites and additional traditional Korean acupuncture treatments were performed. Each session lasted for 10 min and the sessions were carried out twice a week for 5 weeks. The patient's Mini-Rhinoconjunctivitis Quality-of-Life Questionnaire score decreased from 38, at the beginning of treatment, to 23, 3 weeks after the last treatment. The Total Nasal Symptom Score was reduced from six (baseline) to five, 3 weeks after the last treatment. There was significant clinical improvement in the forced expiratory volume in 1 s-from 3.01 to 3.50 l-with discontinuation of the inhaled corticosteroid, and no asthma-related complaints were reported. Further clinical studies investigating the effectiveness of acupuncture for the patients suffering from allergic rhinitis and/or rhinosinusitis with comorbid asthma are needed.

Cupping for treating pain: a systematic review.

The objective of this study was to assess the evidence for or against the effectiveness of cupping as a treatment option for pain. Fourteen databases were searched. Randomized clinical trials (RCTs) testing cupping in patients with pain of any origin were considered. Trials using cupping with or without drawing blood were included, while trials comparing cupping with other treatments of unproven efficacy were excluded. Trials with cupping as concomitant treatment together with other treatments of unproven efficacy were excluded. Trials were also excluded if pain was not a central symptom of the condition. The selection of studies, data extraction and validation were performed independently by three reviewers. Seven RCTs met all the inclusion criteria. Two RCTs suggested significant pain reduction for cupping in low back pain compared with usual care (P < .01) and analgesia (P < .001). Another two RCTs also showed positive effects of cupping in cancer pain (P < .05) and trigeminal neuralgia (P < .01) compared with anticancer drugs and analgesics, respectively. Two RCTs reported favorable effects of cupping on pain in brachialgia compared with usual care (P = .03) or heat pad (P < .001). The other RCT failed to show superior effects of cupping on pain in herpes zoster compared with anti-viral medication (P = .065). Currently there are few RCTs testing the effectiveness of cupping in the management of pain. Most of the existing trials are of poor quality. Therefore, more rigorous studies are required before the effectiveness of cupping for the treatment of pain can be determined.