Dorsal root ganglia control nociceptive input to the central nervous system.

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.

KLHDC7B as a novel diagnostic biomarker in urine exosomal mRNA promotes bladder urothelial carcinoma cell proliferation and migration, inhibits apoptosis.

Bladder cancer is a common kind of urinary system cancer, in which bladder urothelial carcinoma (BLCA) comprises approximately 90% of all bladder cancer types. In our previous study, we discovered KLHDC7B in urine exosomal messenger RNA (mRNA) as a prospective molecular marker for bladder cancer detection. To systematically study the role and mechanism of KLHDC7B in BLCA, we focused on the most common type of BLCA in this study. First, we used RNA sequencing to discover that KLHDC7B was considerably increased in BLCA patients' urine exosomes compared to healthy controls. Then, we validated this result in an independent cohort and identified it as an effective tool for diagnosing and distinguishing high-grade and low-grade BLCA. Finally, we studied the role and mechanism of KLHDC7B in BLCA at the cellular level, providing a functional basis for its expression as a novel laboratory diagnostic biomarker for BLCA exosomal mRNA, which has important theoretical and clinical significance.

Monolithic optical PAM-4 transmitter with autonomous carrier tracking.

We present two single channel optical PAM-4 transmitters, one based on a novel 3-section PN-capacitive micro-ring modulator with on-chip low-power driver and a near-zero power capacitive wavelength locking system and another one based on a 2-section thermally tuned PN micro-ring modulator of the similar size with the same modulator driver. The maximum error-free data-rate of 16 Gb/s and 22 Gb/s at the energy efficiency of 200 fJ/b and 430 fJ/b for the former and the latter transmitters are measured, respectively, and the design trade-offs are discussed. The chips are fabricated in the GlobalFoundries 90 nm CMOS SOI process.

Myricetin Acts as an Inhibitor of Type II NADH Dehydrogenase from Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. RESULTS: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 µM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 µg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. CONCLUSIONS: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.

An item response theory approach to the measurement of working memory capacity.

Complex span tasks are perhaps the most widely used paradigm to measure working memory capacity (WMC). Researchers assume that all types of complex span tasks assess domain-general WM. However, most research supporting this claim comes from factor analysis approaches that do not examine task performance at the item level, thus not allowing comparison of the characteristics of verbal and spatial complex span tasks. Item response theory (IRT) can help determine the extent to which different complex span tasks assess domain-general WM. In the current study, spatial and verbal complex span tasks were examined using IRT. The results revealed differences between verbal and spatial tasks in terms of item difficulty and block difficulty, and showed that most subjects with below-average ability were able to answer most items correctly across all tasks. In line with previous research, the findings suggest that examining domain-general WM by using only one task might elicit skewed scores based on task domain. Further, visuospatial complex span tasks should be prioritized as a measure of WMC if resources are limited.

Flexible long-wave infrared snapshot multispectral imaging with a pixel-level spectral filter array.

This paper proposes and demonstrates a flexible long-wave infrared snapshot multispectral imaging system consisting of a simple re-imaging system and a pixel-level spectral filter array. A six-band multispectral image in the spectral range of 8-12 µm with full width at half maximum of about 0.7 µm each band is acquired in the experiment. The pixel-level multispectral filter array is placed at the primary imaging plane of the re-imaging system instead of directly encapsulated on the detector chip, which diminishes the complexity of pixel-level chip packaging. Furthermore, the proposed method possesses the merit of flexible functions switching between multispectral imaging and intensity imaging by plugging and unplugging the pixel-level spectral filter array. Our approach could be viable for various practical long-wave infrared detection applications.

Linking skeletal muscle aging with osteoporosis by lamin A/C deficiency.

The nuclear lamina protein lamin A/C is a key component of the nuclear envelope. Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of laminopathy-containing diseases, which have features of accelerated aging and osteoporosis. However, the underlying mechanisms for laminopathy-associated osteoporosis remain largely unclear. Here, we provide evidence that loss of lamin A/C in skeletal muscles, but not osteoblast (OB)-lineage cells, results in not only muscle aging-like deficit but also trabecular bone loss, a feature of osteoporosis. The latter is due in large part to elevated bone resorption. Further cellular studies show an increase of osteoclast (OC) differentiation in cocultures of bone marrow macrophages/monocytes (BMMs) and OBs after treatment with the conditioned medium (CM) from lamin A/C-deficient muscle cells. Antibody array screening analysis of the CM proteins identifies interleukin (IL)-6, whose expression is markedly increased in lamin A/C-deficient muscles. Inhibition of IL-6 by its blocking antibody in BMM-OB cocultures diminishes the increase of osteoclastogenesis. Knockout (KO) of IL-6 in muscle lamin A/C-KO mice diminishes the deficits in trabecular bone mass but not muscle. Further mechanistic studies reveal an elevation of cellular senescence marked by senescence-associated beta-galactosidase (SA-ß-gal), p16Ink4a, and p53 in lamin A/C-deficient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phenotype (SASP) and IL-6 expression. Taken together, these results suggest a critical role for skeletal muscle lamin A/C to prevent cellular senescence, IL-6 expression, hyperosteoclastogenesis, and trabecular bone loss, uncovering a pathological mechanism underlying the link between muscle aging/senescence and osteoporosis.

Insights into urinary incontinence after robot-assisted radical prostatectomy: urgent urinary incontinence or stress urinary incontinence.

PURPOSE: Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Few studies have explored the relationships and differences between stress urinary incontinence (SUI) and urgent urinary incontinence (UUI) after RARP. This study aimed to investigate the occurrence rates and risk factors of UUI and SUI in short term after RARP. METHODS: We prospectively included prostate cancer patients who underwent RARP by a single surgeon. Demographics, lower urinary tract function, oncology, and follow-ups were recorded. Occurrence rates and risk factors of UUI and SUI within 3 months after catheter withdrawal were calculated. RESULTS: The study cohort included 363 subjects with a mean age of 66.05 years. The median preoperative International Prostate Symptom Score (IPSS) was 14 (range 0-35), and the median Overactive Bladder Symptom Score (OABSS) was 3 (range 0-14). The occurrence rate of UUI and SUI at 3 months after catheter withdrawal was 8.5% (31/363) and 15.2% (55/363). Nearly all patients with UUI also had SUI. Diabetes history and high OABSS before RARP were independent risk factors for UUI, especially within 1 month after catheter withdrawal. The Gleason Score was an independent risk factor for SUI at 3 months after catheter withdrawal. Additionally, UUI but not SUI might be an influencing factor for decision-making regarding postoperative radiotherapy. CONCLUSION: The occurrence rate of SUI after RARP was persistently higher than that of UUI. Nearly all of the patients with UUI simultaneously had SUI. The risk factors of UUI and SUI after RARP were absolutely different.

Comparison of minimally invasive versus open pelvic organ-preserving radical cystectomy in female patients with bladder cancer: a multicenter propensity score matching analysis.

PURPOSE: To compare the perioperative and oncologic outcomes between minimally invasive pelvic organ-preserving radical cystectomy (MIPOPRC) and open pelvic organ-preserving radical cystectomy (open POPRC) among female patients with bladder cancer (BCa). METHODS: We identified female patients who underwent POPRC for BCa at three centers between January 2006 and April 2018. Female patients who underwent open POPRC were matched with those who underwent MIPOPRC using 1:1 propensity score (PS) matching. The patient demographics and perioperative and oncologic outcomes were evaluated for the comparison between MIPOPRC and open POPRC. RESULTS: Among the 158 patients enrolled, 83 patients underwent MIPOPRC, and 75 underwent open POPRC. A total of 60 MIPOPRC and 60 open POPRC patients were matched successfully. The cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ significantly in the propensity score-weighted cohort (p = 0.297 and p = 0.600, respectively). Subgroup analysis by age and pathologic stage in the matched cohort revealed that CSS and RFS were with no differences among all subgroups. Moreover, multivariable Cox regression analyses showed that the surgical approach (MIPOPRC vs open POPRC) was not a predictor of CSS (p = 0.250). CONCLUSION: MIPOPRC was non-inferior to open POPRC in terms of oncologic outcomes among female patients. MIPOPRC could be technically feasible in selected female patients with BCa.

The predictive value of relative wall thickness on the prognosis of the patients with ST-segment elevation myocardial infarction.

OBJECTIVE: The study aimed to evaluate the prognostic value of relative wall thickness (RWT) in the patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 866 patients with STEMI admitted in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from November 2010 to December 2018 were enrolled in the current study retrospectively. Three methods were used to calculate RWT: RWTPW, RWTIVS+PW and RWTIVS. The included patients were divided according to the median values of RWTPW, RWTIVS+PW, and RWTIVS, respectively. Survival analysis were performed with Kaplan-Meier plot and multivariate Cox proportional hazard model was established to evaluate the adjusted hazard ratio of the three kinds of RWT for all cause death, cardiac death and MACE (major adverse cardiac death). RESULTS: There was no significance for the survival analysis between the low and high groups of RWTPW, RWTIVS+PW and RWTIVS at 30 days and 12 months. Nonetheless, the cumulative incidence of all cause death and cardiac death in the low group of RWTPW and RWTIVS+PW was higher than those in the high group at 60 months. The cumulative incidence of MACE in the low group of RWTPW was higher than the high group at 60 months. Multivariate Cox regression model showed that RWTPW were inversely associated with long-term cardiac death and MACE in STEMI patients. In the subgroup analysis, three calculations of RWT had no predictive value for the patients with anterior myocardial infarction. By contrast, RWTPW was the most stable independent predictor for the long-term outcomes of the patients with non-anterior myocardial infarction. CONCLUSION: RWTPW, RWTIVS+PW and RWTIVS had no predictive value for the long-term clinical outcomes of patients with anterior myocardial infarction, whereas RWTPW was a reliable predictor for all cause death, cardiac death and MACE in patients with non-anterior myocardial infarction.

[Neurobehavioral damage and Th17 cell infiltration in mice exposed to nano carbon black].

OBJECTIVE: The effects of nano-carbon black on neural behavior and Th17 cell infiltration in mice were investigated by establishing a mice model of subacute dynamic inhalation of carbon black aerosol. METHODS: 36 SPF grade male C57BL/6 mice were randomly divided into a control group(clean air), a low carbon black group(15 mg/m~3), and a high carbon black group(30 mg/m~3). Nano-carbon black particles were blown into the dynamic exposure cabinet by aerosol generator for 28 days. Morris water maze test and open field test were used to detect the neural behavior of mice. The pathological changes of prefrontal cortex in mice were observed by HE staining. The proportion of Th17/CD4~+ cells in peripheral blood and brain tissue of mice was detected by flow cytometry. Western blotting was used to detect the protein expression of interleukin(IL)-17 and IL-23 in the prefrontal cortex of mice. RESULTS: The result of open field test showed that compared with the control group, the central area residence time and standing times of mice in the low and high carbon black groups decreased significantly(P<0.05), and the defecation times of mice in the high carbon black group increased significantly(P<0.05). The central area residence time of mice in the high carbon black group was significantly lower than that in the low carbon black group(P<0.05). The Morris water maze result showed that the escape latency of the high carbon black group mice on the 3rd day was significantly higher than that of the control group(P<0.05). Meanwhile, the escape latency of the carbon black group mice on the 4th day was significantly higher than that of the control group(P<0.05). The positioning navigation test showed that the number of mice crossing the platform in the high carbon black group was significantly higher than that in the control group(P<0.05). The HE staining result showed that the neural cells in the prefrontal cortex of the control group mice were round, the cytoplasm was plump and evenly distributed, and the nucleus was clearly visible in an oval shape. The low carbon black group showed that the neural cells were deep staining of nerve cells, blurred structure, and nuclear pyknosis. The high carbon black group further intensified. The flow cytometry result showed that compared with the control group, the percentage of Th17/CD4~+T cells in the peripheral blood of the carbon black group mice was significantly increased, and the high carbon black group mice were significantly higher than the low carbon black group(P<0.05). Meanwhile, the percentage of Th17/CD4~+T cells in the brain tissue of carbon black treated mice significantly increased(P<0.05). The high carbon black group was significantly higher than the low carbon black group(P<0.05). Western blotting result showed that compared with the control group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the carbon black group mice brain tissue was significantly increased(P<0.05). Compared with the low carbon black group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the high carbon black group mice brain tissue was significantly increased(P<0.05). The difference was statistically significant. CONCLUSION: Nano-carbon black exposure can lead to an increase in Th17 cells in peripheral blood and brain tissue of mice, which in turn promotes damage to the prefrontal cortex of mice, and ultimately causes neurobehavioral changes in mice.

Robot-Assisted Radical Prostatectomy Using the KangDuo Surgical Robot-01 System: A Prospective, Single-Center, Single-Arm Clinical Study.

PURPOSE: Our goal was to evaluate the feasibility, safety and effectiveness of the KangDuo Surgical Robot-01 (KD-SR-01) system for robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: This prospective, single-center, single-arm clinical study was conducted from May 2021 to August 2021. Sixteen RARP procedures with the KD-SR-01 system were performed by 1 surgeon. The perioperative and followup data were prospectively recorded. Early oncologic outcomes were assessed according to surgical margin status and continence was defined as no more than 1 pad daily or urine leakage of ≤20 gm by the 24-hour pad weight test. Ergonomics were assessed with the NASA-TLX (National Aeronautics and Space Administration Task Load Index). RESULTS: All cases were completed successfully without conversion to traditional RARP, laparoscopic surgery or open surgery. The median docking time, console time and urethrovesical anastomosis time were 5.9 (range, 2.5-11.5), 87 (range, 70-120) and 14.4 minutes (range, 12.0-25.7), respectively. The median estimated blood loss was 50 ml (range, 10-200). None of patients required intraoperative transfusion. The median postoperative hospital stay was 5 days (range, 4-10). Overall, a positive surgical margin occurred in 4 (25%) patients. No biochemical recurrence occurred within 1 month after surgery. The continence rate was 87.5% (14/16) at 1 month after catheter removal. No severe intraoperative or postoperative complications (Clavien-Dindo grade ≥3) occurred. The surgeon reported a high comfort level with a NASA-TLX global score of 22.7±3.2. CONCLUSIONS: The KD-SR-01 system is feasible, safe and effective for management of localized prostate cancer.

Construction of a novel necroptosis-related lncRNA signature for prognosis prediction in esophageal cancer.

BACKGROUND: Esophageal cancer (EC), one highly malignant gastrointestinal cancer, is the 6th leading cause of cancer-related deaths worldwide. Necroptosis and long non-coding RNA (lncRNA) play important roles in the occurrence and development of EC, but the research on the role of necroptosis-related lncRNA in EC is not conclusive. This study aims to use bioinformatics to investigate the prognostic value of necroptosis-related lncRNA in EC. METHODS: Transcriptome data containing EC and normal samples, and clinical information were obtained from the Cancer Genome Atlas database. 102 necroptosis-related genes were obtained from Kanehisa Laboratories. Necroptosis-related lncRNAs were screened out via univariate, multivariate Cox and the least absolute shrinkage and selection operator regression analyses to construct the risk predictive model. The reliability of the risk model was evaluated mainly through quantitative real-time PCR (qRT-PCR), the receiver operating characteristic (ROC) curves and the constructed nomogram. KEGG pathways were explored in the high- and low-risk groups of EC patients via gene set enrichment analyses (GSEA) software. Immune microenvironment and potential therapeutic agents in risk groups were also analyzed. RESULTS: A 6 necroptosis-related lncRNAs risk model composed of AC022211.2, Z94721.1, AC007991.2, SAMD12-AS1, AL035461.2 and AC051619.4 was established to predict the prognosis level of EC patients. qRT-PCR analysis showed upregulated Z94721.1 and AL035461.2 mRNA levels and downregulated AC051619.4 mRNA level in EC tissues compared with normal tissues. According to clinical characteristics, the patients in the high-risk group had a shorter overall survival than the low-risk group. The ROC curve and nomogram confirmed this model as one independent and predominant predictor. GSEA analysis showed metabolic and immune-related pathways enriched in the risk model. Most of the immune cells and immune checkpoints were positively correlated with the risk model, mainly active in the high-risk group. For the prediction of potential therapeutic drugs, 16 compounds in the high-risk group and 2 compounds in the low-risk group exhibited higher sensitivity. CONCLUSIONS: Our results supported the necroptosis-related lncRNA signature could independently predict prognosis of EC patients, and provided theoretical basis for improving the clinical treatment of EC.

A clinical observational study of effectiveness of a solid coupling medium in extracorporeal shock wave lithotripsy.

This study aimed to investigate clinical effectiveness of stone disintegration by using isolation coupling pad ("icPad") as coupling medium to reduce trapped air pockets during extracorporeal shock wave lithotripsy (ESWL). Patients underwent ESWL between Oct. 2017 and May 2018 were enrolled in this clinical observational study. An electromagnetic lithotripter (Dornier MedTech Europe GmbH Co., Germany) was used in this study. Patients were divided into icPad group P1, P2 and semi-gel group C by different coupling medium. The energy level and total number of shock wave (SW) for group P1 and C was set at level 2 and 3000 and group P2 at level 3 and 2500. The successful stone disintegration rate (SSDR) was determined to evaluate the treatment outcome. All patients were evaluated by KUB film and ultrasonography after 90 days. Complications during ESWL were recorded. A total of 300 patients satisfied the inclusion criteria. There were no significant differences in characteristics of patients and stone among three groups. The corresponding SSDRs for patients in group P1, P2 and C was 73.0%, 73.2% and 55.3%, respectively. The SSDR in group P1 was statistically higher than Group C. Comparing to semi-liquid gel, coupling medium using by icPad could achieve better treatment outcome of stone disintegration in ESWL.

Skimmianine as a novel therapeutic agent suppresses proliferation and migration of human esophageal squamous cell carcinoma via blocking the activation of ERK1/2.

Esophageal squamous cell carcinoma (ESCC), one of the main histopathological subtypes of esophageal cancer (EC), is characterized by high morbidity and mortality. Clinical treatment for ESCC lacks specific molecular targets and effective therapeutic drugs. Skimmianine (SK), one of the natural fluroquinolone alkaloids, is widely present in Rutaceae family plants. Here, we mainly used CCK-8 assay, clone formation, flow cytometry analysis, wound-healing assay, Transwell assay, western blot, quantitative real-time PCR (qRT-PCR), molecular docking analysis, tumor xenograft assay, and immunohistochemistry (IHC) staining to investigate the potential anti-tumor effect of SK on ESCC. We demonstrated that SK inhibited the proliferation of TE-1 and Eca109 cells via inducing the G0/G1 phase cell cycle arrest, prevented the migration and invasion of tumor cells via regulating epithelial-mesenchymal transition (EMT) in vitro. In addition, SK obviously suppressed the growth of xenografted Eca109 tumors in nude mice. The anti-tumor mechanism of SK could be blocking the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. Our basic research suggests that SK can be a potential therapeutic agent for ESCC.

The impact of auditory distraction on reading comprehension: An individual differences investigation.

Background noise disrupts auditory selective attention and impairs performance on cognitive tasks, but the degree to which it is disruptive depends on the task and the individual. According to the load theory of attention and cognitive control, selective attention is influenced by both the perceptual load and the cognitive load of the primary task. Recent studies suggest that hard-to-read font in a reading task may shield attention against background noise and auditory distraction. The current study examined the disruptive effect of background noise on reading comprehension as a function of perceptual load and cognitive load. Perceptual load was manipulated by introducing task disfluency (hard-to-read or easy-to-read font), and cognitive load was manipulated by varying the type of background noise and investigating individual differences in working memory capacity. The results suggest that high perceptual load and high working memory capacity both facilitate reading comprehension. However, contrary to previous research, neither perceptual load nor capacity moderates the disruptive effect of background noise. These results failed to support the generalizability and applicability of the shield effect of perceptual disfluency against auditory distraction during reading but supported the beneficial effect of perceptual disfluency on reading comprehension.

Learning active sensing strategies using a sensory brain-machine interface.

Diverse organisms, from insects to humans, actively seek out sensory information that best informs goal-directed actions. Efficient active sensing requires congruity between sensor properties and motor strategies, as typically honed through evolution. However, it has been difficult to study whether active sensing strategies are also modified with experience. Here, we used a sensory brain-machine interface paradigm, permitting both free behavior and experimental manipulation of sensory feedback, to study learning of active sensing strategies. Rats performed a searching task in a water maze in which the only task-relevant sensory feedback was provided by intracortical microstimulation (ICMS) encoding egocentric bearing to the hidden goal location. The rats learned to use the artificial goal direction sense to find the platform with the same proficiency as natural vision. Manipulation of the acuity of the ICMS feedback revealed distinct search strategy adaptations. Using an optimization model, the different strategies were found to minimize the effort required to extract the most salient task-relevant information. The results demonstrate that animals can adjust motor strategies to match novel sensor properties for efficient goal-directed behavior.

Effectiveness of Sensor-based Rehabilitation in Improving Outcomes in Patients Undergoing Total Knee Arthroplasty.

BACKGROUND: Physical rehabilitation after total knee arthroplasty (TKA) is important for long-term functional recovery. Recently, sensor-based home rehabilitation (SHR) has gained prominence as a promising method that allows monitoring and guidance that is both structured and accessible, compared to traditional methods of physical rehabilitation. Despite the advent of wearable sensor systems, there is a paucity of evidence regarding SHR in the current literature. Thus, this systematic review aimed to evaluate the effect of wearable SHR on post-TKA outcomes. METHODS: We performed a systematic search of three electronic databases from the beginning of record to March 12, 2021. Primary outcomes were patient-reported outcome measures (PROMs) after rehabilitation, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Knee Society Score (KSS). Secondary outcomes were physical activity levels and functional performance including range of motion (ROM) and Timed Up and Go Test (TUG). RESULTS: A total of 16 studies involving 1321 subjects were included. All wearable sensors in our included studies involved a combination of accelerometers, gyroscopes and magnetometers as functional units. These studies reported favourable outcomes for all three PROMs, although the extent of improvement in specific domains varied among studies. Moreover, physical activity in terms of daily steps and time spent on physical activity increased post-rehabilitation. Similarly, there were improvements in ROM and TUG that reflected a favourable post-operative trajectory during rehabilitation. CONCLUSION: SHR is effective for improving subjective and objective outcomes post-TKA. The role of SHR should be evaluated by a dedicated cost-benefit analysis to facilitate its wider adoption in healthcare systems.

Junctophilin-4 facilitates inflammatory signalling at plasma membrane-endoplasmic reticulum junctions in sensory neurons.

KEY POINTS: Rat somatosensory neurons express a junctional protein, junctophilin-4 (JPH4) JPH4 is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the junctions between plasma membrane and endoplasmic reticulum in these neurons. Knockdown of JPH4 impairs endoplasmic reticulum Ca2+ store refill and junctional Ca2+ signalling in sensory neurons. In vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly attenuated experimentally induced inflammatory pain in rats. Junctional nanodomain Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms. ABSTRACT: Junctions of endoplasmic reticulum and plasma membrane (ER-PM junctions) form signalling nanodomains in eukaryotic cells. ER-PM junctions are present in peripheral sensory neurons and are important for the fidelity of G protein coupled receptor (GPCR) signalling. Yet little is known about the assembly, maintenance and physiological role of these junctions in somatosensory transduction. Using fluorescence imaging, proximity ligation, super-resolution microscopy, in vitro and in vivo gene knockdown we demonstrate that a member of the junctophilin protein family, junctophilin-4 (JPH4), is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the ER-PM junctions in rat somatosensory neurons. Thus we show that JPH4 localises to the ER-PM junctional areas and co-clusters with SOCE proteins STIM1 and Orai1 upon ER Ca2+ store depletion. Knockdown of JPH4 impairs SOCE and ER Ca2+ store refill in sensory neurons. Furthermore, we demonstrate a key role of the JPH4 and junctional nanodomain Ca2+ signalling in the pain-like response induced by the inflammatory mediator bradykinin. Indeed, an in vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly shortened the duration of nocifensive behaviour induced by hindpaw injection of bradykinin in rats. Since the ER supplies Ca2+ for the excitatory action of multiple inflammatory mediators, we suggest that junctional nanodomain Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms.

The safety and feasibility of intra-corporeal gastroduodenostomy using a self-pulling and latter transected method (Delta SPLT) in totally laparoscopic distal gastrectomy.

BACKGROUND AND OBJECTIVES: In 2016, the self-pulling and latter transection method (named "Delta SPLT"), a modified delta-shaped gastroduodenostomy (DA) technique for totally laparoscopic distal gastrectomy, was described. Delta SPLT reduced the technical difficulty of the surgery and the quantity of cartridges required with a manageable initial safety profile. Here, the safety and feasibility of this technique are analyzed at 1 year's follow-up. METHODS: The demographic and clinicopathologic profiles, perioperative details, and postoperative outcomes of 45 consecutive patients who underwent Delta SPLT from March 2016 to March 2019 were retrospectively analyzed. The Delta SPLT technique, which consisted of one endoscopic linear stapler and four cartridges each, was used for reconstruction in every case. RESULTS: The mean operative time was 127.1 ± 38.2 min, including a reconstruction duration of 22.6 ± 7.2 min. There were no surgical or anastomotic complications. The mean postoperative stay duration was 5.8 ± 1.2 days, and the morbidity rate was 2.2% with one case of postoperative pneumonia. CONCLUSIONS: The results at the one-year follow-up suggest that Delta SPLT is a safe and feasible procedure. Delta SPLT is characterized by fewer difficulties experienced during surgery, lower surgical costs, it is easy to practice, and it is beneficial for patients who are undergoing gastroduodenostomy.